222 results on '"C, Bouchier"'
Search Results
2. Polymorphisme et chimiorésistance de Plasmodium falciparum au Cambodge
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Marie-Thérèse Ekala, Odile Mercereau-Puijalon, Nimol Kim, C. Bouchier, and Thierry Fandeur
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Infectious Diseases ,Biology - Published
- 2004
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3. Apical left ventricular aneurysm without atrio-ventricular block due to a lamin A/C gene mutation
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Claude Moraine, Gisèle Bonne, Olivier Dubourg, C. Bouchier, Michel Komajda, Pascale Richard, L. Duboscq-Bidot, Sylvain Briault, Jean-François Forissier, Ketty Schwartz, and Claudine Wisnewski
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Adult ,Male ,congenital, hereditary, and neonatal diseases and abnormalities ,medicine.medical_specialty ,Gene mutation ,Sudden cardiac death ,LMNA ,Ventricular Dysfunction, Left ,Internal medicine ,medicine ,Humans ,Heart Aneurysm ,integumentary system ,business.industry ,Dilated cardiomyopathy ,Middle Aged ,Lamin Type A ,medicine.disease ,Pedigree ,Phenotype ,medicine.anatomical_structure ,Left Ventricular Aneurysm ,Ventricle ,Heart failure ,Mutation ,cardiovascular system ,Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,business - Abstract
Background: Mutations in LMNA gene encoding two ubiquitously expressed nuclear proteins, lamins A and C, give rise to up to 7 different pathologies affecting specific tissues. Three of these disorders affect cardiac and/or skeletal muscles with atrio-ventricular conduction disturbances, dilated cardiomyopathy and sudden cardiac death as common features. Results: A new LMNA mutation (1621C>T, R541C) was found in two members of a French family with a history of ventricular rhythm disturbances and an uncommon form of systolic left ventricle dysfunction. The two patients: the proband and his daughter, were affected and exhibited an atypical form of dilated cardiomyopathy with an unexplained left ventricle aneurysm revealed by ventricular rhythm disturbances without atrio-ventricular block. Conclusion: This finding reinforces the highly variable phenotypic expression of LMNA mutation and emphasizes the fact that LMNA mutations can be associated with different cardiac phenotypes.
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- 2003
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4. Functional consequences of anLMNAmutation associated with a new cardiac and non-cardiac phenotype
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Cécile Pascal, Jean-Christophe Charniot, Jean-Yves Artigou, L. Duboscq-Bidot, C. Bouchier, P. Sebillon, Jeffrey Zaketto Salama, Michel Komajda, Michel Desnos, and M. Peuchmaurd
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Adult ,Cardiomyopathy, Dilated ,Male ,Pathology ,medicine.medical_specialty ,DNA Mutational Analysis ,Mutation, Missense ,Emerin ,Thymopoietins ,Biology ,Transfection ,Cell Line ,Desmin ,Dystrophin ,LMNA ,Genetics ,medicine ,Animals ,Humans ,Missense mutation ,Emery–Dreifuss muscular dystrophy ,Muscle, Skeletal ,Myopathy ,Genetics (clinical) ,Family Health ,Myocardium ,Membrane Proteins ,Nuclear Proteins ,Dilated cardiomyopathy ,DNA ,Middle Aged ,Lamin Type A ,medicine.disease ,Immunohistochemistry ,Pedigree ,COS Cells ,Mutation ,Female ,medicine.symptom ,Lamin ,Plasmids ,Limb-girdle muscular dystrophy - Abstract
Heritable dilated cardiomyopathy is a genetically highly heterogeneous disease. To date 17 different chromosomal loci have been described for autosomal dominant forms of dilated cardiomyopathy with or without additional clinical manifestations. Among the 10 mutated genes associated with dilated cardiomyopathy, the lamin A/C (LMNA) gene has been reported in forms associated with conduction-system disease with or without skeletal muscle myopathy. For the first time, we report here a French family affected with a new phenotype composed of an autosomal dominant severe dilated cardiomyopathy with conduction defects or atrial/ventricular arrhythmias, and a specific quadriceps muscle myopathy. In all previously reported cases with both cardiac and neuromuscular involvement, neuromuscular disorders preceded cardiac abnormalities. The screening of the coding sequence of the LMNA gene on all family members was performed and we identified a missense mutation (R377H) in the lamin A/C gene that cosegregated with the disease in the family. Cell transfection experiments showed that the R377H mutation leads to mislocalization of both lamin and emerin. These results were obtained in both muscular (C2C12) and non-muscular cells (COS-7). This new phenotype points out the wide spectrum of neuromuscular and cardiac manifestations associated with lamin A/C mutations, with the functional consequence of this mutation seemingly associated with a disorganization of the lamina.
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- 2003
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5. Mutational analysis of the β- and δ-sarcoglycan genes in a large number of patients with familial and sporadic dilated cardiomyopathy
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Eric Villard, P. Sebillon, N. Sylvius, Philippe Charron, A. Benaiche, C. Bouchier, L. Duboscq-Bidot, and Michel Komajda
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Genetics ,Candidate gene ,education.field_of_study ,Mutation ,Population ,Dilated cardiomyopathy ,Gene mutation ,Biology ,musculoskeletal system ,medicine.disease ,medicine.disease_cause ,Exon ,Idiopathic dilated cardiomyopathy ,medicine ,education ,Genetics (clinical) ,Limb-girdle muscular dystrophy - Abstract
Dilated cardiomyopathy (DCM) is defined by ventricular dilatation associated with impaired contractile function. Approximately one-third of idiopathic dilated cardiomyopathy cases are due to inherited gene mutations. Mutations in the beta- and delta-sarcoglycan genes have been described in limb girdle muscular dystrophy and/or isolated DCM. In this study, the aim was to investigate the prevalence of these genes in isolated DCM. We screened these two genes for mutations in 99 unrelated patients with sporadic or familial DCM. The coding exon and intron-exon boundaries of each gene were amplified by polymerase chain reaction. Mutation analyses were performed by single-strand conformation polymorphism for the beta-sarcoglycan gene and by direct sequencing for the delta-sarcoglycan gene. New polymorphisms, as well as already described ones, were found in these two genes, but none appeared to be responsible for dilated cardiomyopathy. We, therefore, conclude that these genes are not responsible for idiopathic isolated dilated cardiomyopathy in our population. Furthermore, based on previously published and present data, we could estimate the prevalence of delta-sarcoglycan gene mutations to be less than 1% in idiopathic dilated cardiomyopathy, demonstrating that this gene is only marginally implicated in the disease.
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- 2003
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6. Array-based hybridization of Helicobacter pylori isolates to the complete genome sequence of an isolate associated with MALT lymphoma
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Thiberge, J.-M and C. Boursaux-Eude, P. Lehours, M.-A. Dillies, S. Creno, J.-Y. Coppxe9e4 Z. Rouy, A. Lajus, L. Ma, C. Burucoa, A. Ruskonxe9-Foumestraux8 A. Courillon-Mallet, H. De Reuse, I.G. Boneca, D. Lamarque, F. Mxe9graud, J.-C. Delchier, C. Mxe9digue, C. Bouchier, A. Labigne & J. Raymond
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- 2010
7. Irish society of gastroenterology
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E. J. Fitzgerald, A. Chua, C. Clabby, P. W. N. Keeling, J. M. Gilvarry, F. Keeling, O. Fitzgerald, J. F. Fielding, Elizabeth Mathai, T. O’Riordan, A. Tobin, S. Beattie, M. Cafferkey, C. T. Keane, C. O’Morain, P. J. O’Dwyer, A. Hassan, J. J. Murphy, N. J. Higgins, D. Kelly, G. P. McEntee, K. F. McGeeney, J. M. Fitzpatrick, D. P. Halpin, P. M. O’Byme, G. McEntee, T. P. Hermessy, R. B. Stephens, J. P. Hurley, P. Keeling, S. O’Brien, M. Keoghan, N. Afdhal, J. E. Hegarty, P. Burke, M. Sharp, O. Traynor, R. G. Molloy, M. G. O’Riordan, P. Gillen, W. O. Kirwan, E. Mathai, T. Keane, P. T. Byrne, R. Stuart, P. Lawlor, G. O’Sullivan, T. P. J. Hennessy, J. Hourihane, R. Stephens, F. J. Mullan, G. R. Campbell, J. Rowlands, S. T. D. McKelvey, F. I. Mullan, H. K. Wilson, W. Majury, J. Mills, A. J. Cromie, M. J. Kerin, D. O’Farrell, R. P. Waldron, J. G. Johnson, K. C. Trimble, D. P. Nunes, M. G. Courtney, L. Pomeroy, A. G. Shattock, F. M. Mulcahy, D. G. Weir, S. Ah-Kion, N. Noonan, J. Murphy, J. McNulty, M. Casey, M. X. Fitzgerald, B. Waldon, P. T. Cullen, D. Hopwood, D. Sutton, N. Kennedy, F. C. Campbell, N. MacMahon, B. Hogan, J. Murray, J. S. Doyle, J. M. Deasy, J. Carr, C. Bouchier-Hayes, A. P. Cleary, T. N. Walsh, W. F. Gawley, P. M. O’Byrne, M. I. Gleeson, D. T. Calthorpe, B. E. Lane, S. J. Heffernan, H. Sanfey, J. Steer, D. Cottell, M. Steer, T. F. Gorey, N. Nolan, P. Byme, R. Stewart, E. Nolan, E. Jones, M. MacMahon, P. Brennan, E. Carmody, D. Nizar, H. Osbome, R. L. O’Dwyer, F. Stevens, F. McCarthy, A. P. Clery, D. Bouchier-Hayes, S. Crerand, T. M. Feeley, R. Waldron, T. Corrigan, W. Hederman, and F. O’Cormell
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endocrine system ,medicine.medical_specialty ,endocrine system diseases ,business.industry ,Thyroid ,General Medicine ,Dapsone ,medicine.disease ,Asymptomatic ,Gastroenterology ,Anti-thyroid autoantibodies ,Coeliac disease ,medicine.anatomical_structure ,Internal medicine ,Dermatitis herpetiformis ,medicine ,Gluten free ,Thyroid function ,medicine.symptom ,business ,medicine.drug - Abstract
Abnormalities of the thyroid gland are said to be common in patients with dermatitis herpetiformis (DH), treated with dapsone (Thyroid abnormalities in dermatitis herpetiformis. Cunningham andZone, Annals Int.Med. 1985: 102, 194-196). Thepossibility that the goitrogenic effects of dapsone may play a role in this has not been evaluated. We therefore studied thyroid abnormalities in 40 patients with DH, 25 of whom were taking dapsone and 15 of whom were on a gluten free diet alone. All patients were examined clinically for evidence of thyroid dysfunction and blood was drawn for total thyroxine, thyrotrophin levels and thyroid microsomal antibdy titres. Six (24%) of dapsone treated patients had thyroid abnormalities, compared to 1 (7%) of the 15 patients treated with diet alone. Two patients became thyrotoxic when on treatment with dapsone. One patient had myxoedema prior to diagnosis of DH and one developed myxoedema while on dapsone. Two patients with asymptomatic goitres at the time of screening were taking dapsone and one patient on dapsone had thyroid antibodies. Thus it seems likely that the increased incidence of thyroid abnormalities in DH may be related to the effects of the sulphonamide on thyroid function.
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- 1991
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8. Irish association of Rheumatology & Rehabilitation
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A. B. Etwebi, F. R. Comerford, Maire Callaghan, D. Mulherin, A. Whelan, C. Feighery, M. X. FitzGerald, B. Bresnihan, A. L. Bell, G. M. Markey, H. D. Alexander, M. Morris, J. A. McNally, S. O’Byrne, M. Hall, J. T. Cuffe, J. Feely, E. B. Casey, A. de Paor, R. Reilly, Eoin Casey, B. McCormack, G. Kearns, C. Beirne, D. Ryan, G. D. Kearns, E. M. Nuallain, D. J. Reen, D. Kelleher, Anne Murphy, D. Cullen, A. Murphy, G. Keams, D. Foley-Nolan, A. Brady, J. Stack, C. Barry, J. Ennis, R. J. Coughlan, P. Murray, E. Campbell, B. Keogh, J. O’Donoghue, R. Woods, L. Choudhry, P. Byrne, C. J. McCarthy, Marian Regan, J. McCarthy, R. J. Coughlin, C. McCarthy, R. Coughlan, T. J. Sant, S. Healy, E. Healy, S. Sant, J. Tyrrell, M. Barry, G. Murphy, D. Veale, S. Rogers, L. Barnes, O. FitzGerald, J. Cooney, R. McQuillan, A. Leahy, J. Barton, M. McMahon, C. Bouchier-Hayes, G. Courtney, J. S. Doyle, A. J. Taggart, F. McEvoy, D. Heylings, P. McMillin, J. Hassan, G. Yarani, Eva Doherty, Catherine Harden, J. Jackson, G. Yanni, B. Breshihan, and B. Shaw
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medicine.medical_specialty ,Rehabilitation ,business.industry ,medicine.medical_treatment ,General Medicine ,language.human_language ,Rheumatology ,Irish ,Internal medicine ,Family medicine ,language ,Physical therapy ,Medicine ,business - Published
- 1991
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9. [Chemoresistance and polymorphism in falciparum malaria in Cambodia]
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N, Kim, C, Bouchier, M T, Ekala, O, Mercereau-Puijalon, and T, Fandeur
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Polymorphism, Genetic ,Mutation ,Plasmodium falciparum ,Drug Resistance ,Cambodia - Published
- 2005
10. Expanding the phenotype of LMNA mutations in dilated cardiomyopathy and functional consequences of these mutations
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V Drouin-Garraud, Eric Villard, C. Bouchier, A. Benaiche, P. Sebillon, Gisèle Bonne, Ketty Schwartz, K Ahamed, Philippe Charron, Alain Millaire, L D Bidot, G Desrumeaux, J-C Charniot, and Michel Komajda
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Adult ,Cardiomyopathy, Dilated ,Male ,congenital, hereditary, and neonatal diseases and abnormalities ,Adolescent ,Population ,DNA Mutational Analysis ,Cardiomyopathy ,Biology ,medicine.disease_cause ,Transfection ,Cell Line ,LMNA ,Myoblasts ,Mice ,Chlorocebus aethiops ,Genetics ,medicine ,Missense mutation ,Animals ,Humans ,education ,Myopathy ,Child ,Genetics (clinical) ,Aged ,education.field_of_study ,Mutation ,integumentary system ,Reverse Transcriptase Polymerase Chain Reaction ,Dilated cardiomyopathy ,Middle Aged ,medicine.disease ,Lamin Type A ,Pedigree ,Survival Rate ,Phenotype ,embryonic structures ,COS Cells ,Female ,Original Article ,medicine.symptom ,Haploinsufficiency - Abstract
Aims: Mutations in the lamin A/C gene (LMNA) have been reported to be involved in dilated cardiomyopathy (DCM) associated with conduction system disease and/or skeletal myopathy. The aim of this study was to perform a mutational analysis of LMNA in a large white population of patients affected by dilated cardiomyopathy with or without associated symptoms. Methods: We performed screening of the coding sequence of LMNA on DNA samples from 66 index cases, and carried out cell transfection experiments to examine the functional consequences of the mutations identified. Results: A new missense (E161K) mutation was identified in a family with early atrial fibrillation and a previously described (R377H) mutation in another family with a quadriceps myopathy associated with DCM. A new mutation (28insA) leading to a premature stop codon was identified in a family affected by DCM with conduction defects. No mutation in LMNA was found in cases with isolated dilated cardiomyopathy. Functional analyses have identified potential physiopathological mechanisms involving identified mutations, such as haploinsufficiency (28insA) or intermediate filament disorganisation (E161K, R377H). Conclusion: For the first time, a specific phenotype characterised by early atrial fibrillation is associated with LMNA mutation. Conversely, mutations in LMNA appear as a rare cause of isolated dilated cardiomyopathy. The variable phenotypes observed in LMNA-DCM might be explained by the variability of functional consequences of LMNA mutations.
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- 2003
11. Epidemiology of desmin and cardiac actin gene mutations in a european population of dilated cardiomyopathy
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A. Benaiche, F. Tesson, Antonello Gavazzi, L. Dubosq-Bidot, M. Peuchmaurd, Eloisa Arbustini, L. Mangin, N. Sylvius, Luigi Tavazzi, Michel Komajda, Andrea Pilotto, C. Bouchier, and Philippe Charron
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Cardiomyopathy, Dilated ,Cardiomyopathy ,Gene mutation ,medicine.disease_cause ,Desmin ,Gene Frequency ,medicine ,Missense mutation ,Humans ,Genetic Testing ,Myopathy ,Polymorphism, Single-Stranded Conformational ,Genetics ,Mutation ,Base Sequence ,business.industry ,Myocardium ,Dilated cardiomyopathy ,medicine.disease ,Actins ,Europe ,Restriction fragment length polymorphism ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business - Abstract
Aims Although dilated cardiomyopathy is the most frequent form of cardiomyopathy, its aetiology is still poorly understood. In about 20–30% of cases the disease is familial with a large predominance of autosomal dominant transmission. Ten different chromosomal loci have been described for autosomal dominant forms of dilated cardiomyopathy. Only two genes have been associated with pure forms (without myopathy and/or conduction disorders) of the disease, the cardiac actin and the desmin genes. Our aim was to determine the proportion of dilated cardiomyopathy affected individuals carrying a mutation in one of these two genes. Methods and Results We performed (1) a systematic polymerase chain reaction-SSCP-sequencing screening of the coding sequences of cardiac actin on DNA samples from 43 probands of dilated cardiomyopathy families and 43 sporadic cases; (2) a systematic polymerase chain reaction-SSCP-sequencing screening of the coding sequences of desmin combined with a search for the described missense mutation (Ile451Met) by restriction fragment length polymorphism analysis on DNA samples from 41 probands of dilated cardiomyopathy families and 22 sporadic cases. Conclusion None of the patients presents a mutation in any of these two genes. Consequently, the proportion of European dilated cardiomyopathy affected individuals bearing a mutation in (1) the cardiac actin gene is less than 1·2%, (2) the desmin gene is less than 1·6%.
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- 2000
12. Isolation from a human seminal vesicle library of the cDNA for gp17, a CD4 binding factor
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M, Autiero, C, Bouchier, S, Basmaciogullari, P, Zaborski, S, el Marhomy, M, Martin, J, Guardiola, and D, Piatier-Tonneau
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Male ,Base Sequence ,Molecular Sequence Data ,Membrane Transport Proteins ,Seminal Vesicles ,Blotting, Northern ,Neoplasm Proteins ,Apolipoproteins ,CD4 Antigens ,Escherichia coli ,Humans ,Amino Acid Sequence ,RNA, Messenger ,Carrier Proteins ,Apolipoproteins D ,Gene Library ,Glycoproteins - Published
- 1997
13. Idiopathic dilated cardiomyopathy: lack of association with haemochromatosis gene in the CARDIGENE study
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Ketty Schwartz, B Grandchamp, Michel Desnos, Michel Komajda, Gérard Roizès, Laurence Tiret, Richard Dorent, Viviane Nicaud, C. Bouchier, and G. Hetet
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Cardiomyopathy, Dilated ,Male ,Heterozygote ,congenital, hereditary, and neonatal diseases and abnormalities ,medicine.medical_specialty ,Genotype ,Disease ,Compound heterozygosity ,Gastroenterology ,Scientific Letters ,Internal medicine ,Idiopathic dilated cardiomyopathy ,Humans ,Medicine ,Gene ,Polymorphism, Genetic ,business.industry ,nutritional and metabolic diseases ,Heterozygote advantage ,Dilated cardiomyopathy ,Middle Aged ,medicine.disease ,White (mutation) ,Case-Control Studies ,Heart failure ,Mutation ,Cardiology ,Female ,Hemochromatosis ,Cardiology and Cardiovascular Medicine ,business - Abstract
The hereditary haemochromatosis gene (HFE) has recently been proposed as a disease modifying gene.1 The rationale is that two common mutations of the HFE gene (C282Y and H63D) are found in a majority of patients with genetic haemochromatosis who are either homozygotes (C282Y/C282Y) or compound heterozygotes (C282Y/H63D). These mutations have been shown to contribute to more subtle modifications of iron homeostasis at the heterozygous state.2 In turn, iron may predispose to myocardial damage through the production of activated oxygen species. Recently, Mahon and colleagues have reported an association between the H63D mutation and idiopathic dilated cardiomyopathy (IDCM).3 In this study, 207 unrelated white patients with dilated cardiomyopathy and 200 controls were tested for HFE C282Y and H63D mutations. An increased proportion of H63D heterozygotes was found among patients (36%) as compared to the control group (27%). No association was found with C282Y mutation and as the H63D mutation had a relatively minor effect on iron status, these authors proposed that this association may be …
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- 2001
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14. 151 Apical left ventricular aneurysm without atrio-ventricular block due to a lamin A/C gene mutation
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J FORISSIER, C BOUCHIER, G BONNE, L DUBOSCQBIDOT, P RICHARD, S BRIAULT, C MORAINE, O DUBOURG, K SCHWARTZ, and M KOMAJDA
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Cardiology and Cardiovascular Medicine - Published
- 2003
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15. Epidemiology of cardiac actin and desmin gene mutations in a European population of dilated cardiomyopathy
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Luigi Tavazzi, P. Andrea, Eloisa Arbustini, L. Mangin, Philippe Charron, M. Peuchmaurd, F. Tesson, A. Benaiche, N. Sylvius, Antonello Gavazzi, C. Bouchier, Michel Komajda, and L. Duboscq-Bidot
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medicine.medical_specialty ,business.industry ,Dilated cardiomyopathy ,European population ,medicine.disease ,Internal medicine ,Heart failure ,Epidemiology ,medicine ,Cardiology ,Desmin ,Cardiology and Cardiovascular Medicine ,business ,Actin - Published
- 2000
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16. A New Locus for Autosomal Dominant Dilated Cardiomyopathy Identified on Chromosome 6q12-q16
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A. Benaiche, Jacques S. Beckmann, Michel Komajda, Philippe Charron, L. Mangin, M. Peuchmaurd, F. Tesson, C. Gayet, C. Bouchier, N. Sylvius, L. Duboscq-Bidot, and Josué Feingold
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Adult ,Cardiomyopathy, Dilated ,Genetic Markers ,Male ,Candidate gene ,Adolescent ,Molecular Sequence Data ,Locus (genetics) ,Biology ,Genetic determinism ,Malate Dehydrogenase ,Genetic linkage ,Report ,Genetics ,medicine ,Humans ,Genetics(clinical) ,cardiovascular diseases ,Gene ,Polymorphism, Single-Stranded Conformational ,Genetics (clinical) ,Aged ,Genes, Dominant ,Recombination, Genetic ,Calcium-Binding Proteins ,Haplotype ,Chromosome Mapping ,Dilated cardiomyopathy ,Middle Aged ,medicine.disease ,Pedigree ,Haplotypes ,Solubility ,Genetic marker ,cardiovascular system ,Chromosomes, Human, Pair 6 ,Female ,France ,Laminin ,Lod Score - Abstract
Dilated cardiomyopathy (DCM) is a heart-muscle disease characterized by ventricular dilatation and impaired heart contraction and is heterogeneous both clinically and genetically. To date, 12 candidate disease loci have been described for autosomal dominant DCM. We report the identification of a new locus on chromosome 6q12-16 in a French family with 9 individuals affected by the pure form of autosomal dominant DCM. This locus was found by using a genomewide search after exclusion of all reported disease loci and genes for DCM. The maximum pairwise LOD score was 3.52 at recombination fraction 0.0 for markers D6S1644 and D6S1694. Haplotype construction delineated a region of 16.4 cM between markers D6S1627 and D6S1716. This locus does not overlap with two other disease loci that have been described in nonpure forms of DCM and have been mapped on 6q23-24 and 6q23. The phospholamban, malic enzyme 1-soluble, and laminin-alpha4 genes were excluded as candidate genes, using single-strand conformation polymorphism or linkage analysis.
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17. Expression of tubulin, GFAP and of their encoding mRNAs during the proliferation and differentiation of cultured astrocytes
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C. Bouchier, Jacques Nunez, G. Le Prince, C. Charriere-Bertrand, Marcienne Tardy, and C. Fages
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Messenger RNA ,Forskolin ,biology ,Glial fibrillary acidic protein ,Cell Biology ,Molecular biology ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,Tubulin ,medicine.anatomical_structure ,chemistry ,Cell culture ,Gene expression ,biology.protein ,medicine ,Northern blot ,Astrocyte - Abstract
The expression of tubulin, of glial fibrillary acidic protein of their encoding mRNAs were studied in primary cultures of mouse astrocytes. The effects of dibutyryl cyclic AMP on these parameters were also analyzed. (1) The concentration of both α- and β-tubulin chains markedly increased (3-fold) between 7 and 12 days of culture and then remained at the same high value at later stages. In contrast α-tubulin mRNA concentration remained constant throughout the same culture period. (2) Glial fibrillary acidic protein concentration increased steadily reaching a 4-fold higher value at the end of the same culture period. The glial fibrillary acidic protein mRNA increased 3-fold during the first 2 weeks of culture, leveled off at day 18 and then decreased steadily returning to low values (3-fold decrease) at later stages. (3) Addition for 2 days, at day 5 or 19 of the culture, of either dibutyryl cyclic AMP or forskolin remained without effect on tubulin concentration whereas a 50% decrease in α-tubulin mRNA was observed. In the same conditions the effects of these drugs on glial fibrillary acidic protein and its mRNA were not significant. These results suggest that the increase in tubulin concentration seen between days 7 and 12, as well as that of glial fibrillary acidic protein observed during the last weeks of the culture, are not secondary to an increase either of the rate of transcription or of the stability of their encoding mRNAs.
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- 1988
18. Crotoxin, half-century of investigations on a phospholipase A2 neurotoxin
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C, Bon, C, Bouchier, V, Choumet, G, Faure, M S, Jiang, M P, Lambezat, F, Radvanyi, and B, Saliou
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Phospholipases A2 ,Molecular Structure ,Neuromuscular Junction ,Drug Synergism ,Crotoxin ,Synaptic Transmission ,Phospholipases A - Abstract
Crotoxin, the major toxic component of the South American rattlesnake, Crotalus durissus terrificus, is a neurotoxic phospholipase A2 which exerts its pathophysiological action by blocking the neuromuscular transmission. Crotoxin acts primarily by altering the acetylcholine release from the nerves terminals through a mechanism which has not yet been elucidated. It also acts on postsynaptic membranes by stabilizing the acetylcholine receptor in an inactive conformation very similar to the desensitized state. Crotoxin is made of two dissimilar subunits: a basic and weakly toxic phospholipase A2 component-B, and an acidic and non toxic component-A which does not possess any enzymatic activity. Binding experiments showed that crotoxin subunits dissociate when crotoxin interacts with biological membranes: Component-B binds, whereas component-A appears free in solution. The phospholipase A2 subunit binds in a non saturable, non specific manner, on any kind of biological membranes, whereas in the presence of component-A it interacts only with a limited number of high affinity binding sites present on synaptic membranes but not on erythrocyte membranes. Although the target site (acceptor) of crotoxin has not yet been formally identified, binding experiments carried out with small unilamellar phospholipid vesicles of different compositions indicate that some negatively charged phospholipids like mono and diphosphoinositide phosphates might be an important component of crotoxin acceptor site. Crotoxin is in fact a mixture of several isoforms which have very similar but not identical polypeptide sequences. An individual Crotalus durissus terrificus snake is able to synthesize several crotoxin isoforms which may result of the expression of several isogenes and/or of post-translational events. When compared in quantitative manner, the crotoxin isoforms slightly but significantly differ in their enzymatic and pharmacological properties. Finally, immunochemical investigations carried out with polyclonal antibodies prepared against both crotoxin subunits, showed that non precipitating anti-component-B- antibodies (Fab) inhibit the phospholipase A2 activity of crotoxin and neutralize its lethal potency, suggesting that the catalytic and toxic sites of crotoxin are closely related.
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- 1989
19. Genetic and functional abnormalities of the melatonin biosynthesis pathway in patients with bipolar disorder
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Sarah Moreno, Marion Leboyer, Frank Bellivier, Sven Cichon, Bruno Etain, Stéphane Jamain, Cécile Pagan, Thomas W. Mühleisen, Flavie Mathieu, Jasmine Deshommes, Jean-Pierre Kahn, Thomas Bourgeron, Katia Le Dudal, Anne Dumaine, Khaled Moustafa, Jean-Marie Launay, Hany Goubran-Botros, Chantal Henry, Laetitia Francelle, Fondation FondaMental [Créteil], Psychiatrie génétique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Mondor de Recherche Biomédicale, Université Paris-Est (UPE), Gènes, Synapses et Cognition, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Hôpital Lariboisière, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 (UPD7), Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Institut Pasteur [Paris], CIC - CHU Henri Mondor, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), University of Bonn, Research Center Juelich, This work was supported by the Institut Pasteur, the Institut National pour la Recherche Médicale (INSERM), the Assistance Publique des Hôpitaux de Paris (AP-HP), the Agence Nationale pour la Recherche (ANR – Project Manage_BPAD), the Fondation pour la Recherche sur le Cerveau (FRC), and the Réseau Thématique de Recherche et de Soin en Santé Mentale (Fondation FondaMental)., We thank the patients for participating in this study. We thank the cell bank of Cochin Hospital (J. Chelly). We thank C. Bouchier and S. Duthoy for the use of sequencing facilities at the Génopole Pasteur, B. Costes and N. Martin at the Genomic platform of the IMRB (M. Gossens), A. Hchikat, L. Margarit and G. Rouffet for technical assistance. We thank E. Abadie, C. Bulach, B. Cochet, M.J. Pereira Gomes, A. Raust, R. Cohen and O. Elgrabli-Wajsbrot for their assistance., ANR-06-NEURO-0026,MANAGE_BPAD,Approche multidisciplinaire incluant la génétique, la biochimie et la neuroimagerie pour l'exploration du trouble bipolaire(2006), Gènes, Synapses et Cognition (CNRS - UMR3571 ), Université Paris Diderot - Paris 7 (UPD7)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), ANR-06-NEUR-0026,MANAGE_BPAS,Approche multidisciplinaire incluant la génétique, la biochimie et la neuroimagerie pour l'exploration du trouble bipolaire(2006), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), and Universität Bonn = University of Bonn
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Male ,Bipolar Disorder ,Transcription, Genetic ,[SDV]Life Sciences [q-bio] ,DNA Mutational Analysis ,[SCCO]Cognitive science ,0302 clinical medicine ,Gene Frequency ,MESH: Bipolar Disorder ,Missense mutation ,MESH: DNA Mutational Analysis ,Promoter Regions, Genetic ,Cells, Cultured ,Genetics (clinical) ,Melatonin ,MESH: Melatonin ,MESH: Genetic Association Studies ,MESH: Acetylserotonin O-Methyltransferase ,MESH: Statistics, Nonparametric ,MESH: Polymorphism, Single Nucleotide ,MESH: Genetic Predisposition to Disease ,General Medicine ,MESH: Case-Control Studies ,Female ,medicine.drug ,MESH: Cells, Cultured ,Acetylserotonin O-Methyltransferase ,medicine.medical_specialty ,Mutation, Missense ,Biology ,Polymorphism, Single Nucleotide ,Statistics, Nonparametric ,03 medical and health sciences ,Internal medicine ,MESH: Promoter Regions, Genetic ,Genetics ,medicine ,MESH: Gene Frequency ,Humans ,Genetic Predisposition to Disease ,Circadian rhythm ,Bipolar disorder ,Molecular Biology ,Allele frequency ,Gene ,Genetic Association Studies ,MESH: Mutation, Missense ,MESH: Humans ,Precursor Cells, B-Lymphoid ,MESH: Transcription, Genetic ,Haplotype ,Case-control study ,MESH: Haplotypes ,medicine.disease ,MESH: Male ,030227 psychiatry ,Endocrinology ,Haplotypes ,MESH: Precursor Cells, B-Lymphoid ,Case-Control Studies ,MESH: Female ,030217 neurology & neurosurgery ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
International audience; Patients affected by bipolar disorder (BD) frequently report abnormalities in sleep/wake cycles. In addition, they showed abnormal oscillating melatonin secretion, a key regulator of circadian rhythms and sleep patterns. The acetylserotonin O-methyltransferase (ASMT) is a key enzyme of the melatonin biosynthesis and has recently been associated with psychiatric disorders such as autism spectrum disorders and depression. In this paper, we analysed rare and common variants of ASMT in patients with BD and unaffected control subjects and performed functional analysis of these variants by assaying the ASMT activity in their B-lymphoblastoid cell lines. We sequenced the coding and the regulatory regions of the gene in a discovery sample of 345 patients with BD and 220 controls. We performed an association study on this discovery sample using common variants located in the promoter region and showed that rs4446909 was significantly associated with BD (P= 0.01) and associated with a lower mRNA level (P< 10(-4)) and a lower enzymatic activity (P< 0.05) of ASMT. A replication study and a meta-analysis using 480 independent patients with BD and 672 controls confirmed the significant association between rs4446909 and BD (P= 0.002). These results correlate with the general lower ASMT enzymatic activity observed in patients with BD (P= 0.001) compared with controls. Finally, several deleterious ASMT mutations identified in patients were associated with low ASMT activity (P= 0.01). In this study, we determined how rare and common variations in ASMT might play a role in BD vulnerability and suggest a general role of melatonin as susceptibility factor for BD.
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- 2012
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20. Screening of Escherichia coli Species Biodiversity Reveals New Biofilm-Associated Antiadhesion Polysaccharides
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Olaya Rendueles, Patricia Latour-Lambert, Erick Denamur, Julie Magnus, Jean-Marc Ghigo, Thierry Fontaine, Laetitia Travier, Génétique des Biofilms, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Aspergillus, Institut Pasteur [Paris] (IP), Ecologie et Evolution des Microorganismes (EEM), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), O.R. was supported by a fellowship from the Network of Excellence EuroPathogenomics, European Community grant LSHB-CT-2005-512061. L.T. was an ANR fellow (ERA-NET EuroPathogenomics). This work was supported by a grant from the Région Île-de-France (DIM Malinf)., We thank C. Bouchier, P. Glaser, and L. Frangeul (Genopole, Institut Pasteur, Paris, France), Zoe Rouy (Genoscope, Évry, France), and C. Buchrieser (Intracellular Bacteria Biology Unit) for their help during genome sequencing and analyses. We are grateful to N. Henry for her help in the determination of surface contact angles. We thank C. Beloin, S. Létoffé, J. Valle, S. Chalabaev, and C. Forestier for helpful discussions and critical reading of the manuscript., European Project: 512061,Network of Excellence EuroPathoGenomics, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris], and Université Paris Diderot - Paris 7 (UPD7)-Université Paris 13 (UP13)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)
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Staphylococcus aureus ,[SDV]Life Sciences [q-bio] ,Microbial metabolism ,Bacterial growth ,medicine.disease_cause ,Polysaccharide ,Microbiology ,Bacterial Adhesion ,03 medical and health sciences ,Virology ,medicine ,Escherichia coli ,Humans ,Pathogen ,030304 developmental biology ,chemistry.chemical_classification ,0303 health sciences ,biology ,030306 microbiology ,Polysaccharides, Bacterial ,Biofilm ,biochemical phenomena, metabolism, and nutrition ,biology.organism_classification ,QR1-502 ,Anti-Bacterial Agents ,[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology ,chemistry ,Biofilms ,Bacteria ,Research Article - Abstract
Bacterial biofilms often form multispecies communities in which complex but ill-understood competition and coop-eration interactions occur. In light of the profound physiological modifications associated with this lifestyle, we hypothesizedthat the biofilm environment might represent an untapped source of natural bioactive molecules interfering with bacterial adhe-sion or biofilm formation. We produced cell-free solutions extracted fromin vitromature biofilms formed by 122 naturalEsche-richia coliisolates, and we screened these biofilm extracts for antiadhesion molecules active on a panel of Gram-positive andGram-negative bacteria. Using this approach, we showed that 20% of the tested biofilm extracts contained molecules that antag-onize bacterial growth or adhesion. We characterized a compound, produced by a commensal animalE. colistrain, for whichactivity is detected only in biofilm extract. Biochemical and genetic analyses showed that this compound corresponds to a newtype of released high-molecular-weight polysaccharide whose biofilm-associated production is regulated by the RfaH protein.We demonstrated that the antiadhesion activity of this polysaccharide was restricted to Gram-positive bacteria and that its pro-duction reduced susceptibility to invasion and provided rapid exclusion ofStaphylococcus aureusfrom mixedE. coliandS. au-reusbiofilms. Our results therefore demonstrate that biofilms contain molecules that contribute to the dynamics of mixed bacte-rial communities and that are not or only poorly detected in unconcentrated planktonic supernatants. Systematic identificationof these compounds could lead to strategies that limit pathogen surface colonization and reduce the burden associated with thedevelopment of bacterial biofilms on medical devices., mBio, 2 (3), ISSN:2150-7511, ISSN:2161-2129
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- 2011
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21. ViralORFeome: an integrated database to generate a versatile collection of viral ORFs
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Gregory Neveu, Laurent Jacotot, Patrice Andre, Vincent Navratil, Chantal Rabourdin-Combe, Marianne Lucas-Hourani, Anne Aublin-Gex, Frédéric Tangy, Laurène Meyniel, M. Le Breton, Yves Jacob, A. Guironnet-Paquet, Vincent Lotteau, Pierre-Olivier Vidalain, Michel Favre, Gilbert Deléage, A Chaboud, Johann Pellet, Christophe Combet, Lionel Tafforeau, Grégory Caignard, Sebastien Delmotte, Thibault Chantier, Patricia Cassonnet, Alexandre Deloire, Philippe Vaglio, Christian Gautier, Caroline Demeret, Guillaume Achaz, Immunité infection vaccination (I2V), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), Génomique Virale et Vaccination, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Rétrovirus et Pathologie Comparée (RPC), Institut National de la Recherche Agronomique (INRA)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Ecole Nationale Vétérinaire de Lyon (ENVL), BioSciences Lyon-Gerland (BLG), École normale supérieure de Lyon (ENS de Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Modul-Bio, Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Génétique, Papillomavirus et Cancer Humain, Institut Pasteur [Paris] (IP), Reproduction et développement des plantes (RDP), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Baobab, Département PEGASE [LBBE] (PEGASE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Institut de biologie et chimie des protéines [Lyon] (IBCP), The Institut National de la Santé et de la Recherche Médicale, the Institut National de la Recherche Agronomique, the Association de la Recherche contre le Cancer (3731XA0531F and 4867), the Ligue Nationale Contre le Cancer (RS07/75-75), the Agence Nationale de la Recherche (EPI-HPV-3D), the French Ministry of Industry, the Institut Pasteur, the Centre National de la Recherche Scientifique (Maladies Infectieuses Emergentes to P.O.V., G.C. and F.T.). Funding for open access charge: Institut Pasteur., We thank all members of PF1-Pasteur Genopole sequencing core facility, in particular C. Bouchier and C. Gouyette. We thank Drs Marie-Louise Michel, Charles M. Rice, Kaoru Takeuchi, T. Fabian Wild and Ali Amara for providing RNA or DNA templates used to build viral ORF clones. We also thank Eric Coissac for providing SQL codes, ANR-07-MIME-0009,EPI-HPV-3D,Vers la compréhension fonctionelle et structurale de l'interactome cellulaire des protéines précoces des Papilloma Virus Humains.(2007), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-École pratique des hautes études (EPHE)-Université Claude Bernard Lyon 1 (UCBL), École normale supérieure - Lyon (ENS Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Institut Pasteur [Paris], Gau, Mireille, Microbiologie, immunologie et maladies émergentes - Vers la compréhension fonctionelle et structurale de l'interactome cellulaire des protéines précoces des Papilloma Virus Humains. - - EPI-HPV-3D2007 - ANR-07-MIME-0009 - MIME - VALID, and Institut National de la Recherche Agronomique (INRA)-École pratique des hautes études (EPHE)
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Genes, Viral ,Cloning ,Molecular ,Computational Biology ,Databases ,Genetic ,Nucleic Acid ,Protein ,Genes ,Viral ,Genetic Techniques ,Genome ,Information Storage and Retrieval ,Internet ,Open Reading Frames ,Protein Structure ,Tertiary ,Software ,User-Computer Interface ,viruses ,MESH: Protein Structure, Tertiary ,Plasmid ,Databases, Genetic ,ORFS ,Cloning, Molecular ,ORFeome ,Databases, Protein ,MESH: Databases, Genetic ,Genetics ,0303 health sciences ,MESH: Genes, Viral ,030302 biochemistry & molecular biology ,Microbiology and Parasitology ,Articles ,Microbiologie et Parasitologie ,3. Good health ,MESH: Internet ,[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology ,Proteome ,MESH: Genome, Viral ,Databases, Nucleic Acid ,Biologie ,MESH: Computational Biology ,MESH: Databases, Protein ,Computational Biology -- methods -- trends ,Information Storage and Retrieval -- methods ,Genome, Viral ,Biology ,MESH: Databases, Nucleic Acid ,03 medical and health sciences ,MESH: Software ,MESH: Cloning, Molecular ,[SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology ,Gene ,030304 developmental biology ,MESH: User-Computer Interface ,MESH: Information Storage and Retrieval ,MESH: Open Reading Frames ,Protein Structure, Tertiary ,Open reading frame ,MESH: Genetic Techniques - Abstract
Large collections of protein-encoding open reading frames (ORFs) established in a versatile recombination-based cloning system have been instrumental to study protein functions in high-throughput assays. Such 'ORFeome' resources have been developed for several organisms but in virology, plasmid collections covering a significant fraction of the virosphere are still needed. In this perspective, we present ViralORFeome 1.0 (http://www.viralorfeome.com), an open-access database and management system that provides an integrated set of bioinformatic tools to clone viral ORFs in the Gateway(R) system. ViralORFeome provides a convenient interface to navigate through virus genome sequences, to design ORF-specific cloning primers, to validate the sequence of generated constructs and to browse established collections of virus ORFs. Most importantly, ViralORFeome has been designed to manage all possible variants or mutants of a given ORF so that the cloning procedure can be applied to any emerging virus strain. A subset of plasmid constructs generated with ViralORFeome platform has been tested with success for heterologous protein expression in different expression systems at proteome scale. ViralORFeome should provide our community with a framework to establish a large collection of virus ORF clones, an instrumental resource to determine functions, activities and binding partners of viral proteins., Journal Article, Research Support, Non-U.S. Gov't, info:eu-repo/semantics/published
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- 2010
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22. Genotype determination in Moroccan hepatitis B chronic carriers
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Lahsen Wakrim, Mohammed Hassar, Jalal Nourlil, Pascal Pineau, Agnès Marchio, Christian Trepo, Abdelouhad El Malki, Isabelle Chemin, Soumaya Benjelloun, Anne Dejean, Abdelaziz Chafik, Sayeh Ezzikouri, Institut Pasteur du Maroc, Réseau International des Instituts Pasteur (RIIP), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Faculté des Sciences [El Jadida. Maroc], Université Chouaib Doukkali (UCD), Organisation Nucléaire et Oncogenèse / Nuclear Organization and Oncogenesis, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Virus des hépatites et pathologies associées, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), We are particularly grateful to Helene Norder and L. Vitvitski-Trepo for critical reading of Manuscript and also C. Bouchier and the personnel of the Genomic Plate-Forme at the Institut Pasteur de Paris. We also thank Jean-Pierre Vartanian for its help in phylogenetic analysis. Finally, we would like to thank L. Radoshevich for her critical review of the manuscript, and Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)
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MESH: Hepatitis B, Chronic / genetics ,Genes, Viral ,Chronic liver disease ,medicine.disease_cause ,MESH: Hepatitis B virus / genetics ,0302 clinical medicine ,Genotype ,MESH: Hepatitis B, Chronic / virology ,Prevalence ,MESH: Phylogeny ,Phylogeny ,MESH: Genotype ,0303 health sciences ,MESH: Genes, Viral ,virus diseases ,Hepatitis B ,3. Good health ,Morocco ,Infectious Diseases ,HBeAg ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,030211 gastroenterology & hepatology ,Restriction fragment length polymorphism ,Antibody ,MESH: DNA, Viral / analysis ,medicine.drug ,Microbiology (medical) ,Heterozygote ,Hepatitis B virus ,Moroccan ,Biology ,Microbiology ,03 medical and health sciences ,Phylogenetic ,Hepatitis B, Chronic ,Genetics ,medicine ,Humans ,Genotype D ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,030304 developmental biology ,MESH: Humans ,Nucleoside analogue ,[SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology ,medicine.disease ,Virology ,digestive system diseases ,MESH: Morocco ,Immunology ,DNA, Viral ,biology.protein ,MESH: Heterozygote - Abstract
Background In Morocco, chronic liver disease related to hepatitis B virus (HBV) is a public health burden. Treatment of chronic hepatitis B is often complicated by the appearance of escape mutants after treatment with nucleoside analogs, especially with genotypes responsible for the more severe form of the disease. Objectives In the present study we investigate the prevalence of the different HBV genotypes in Morocco since no previous careful study has been attempted. Methods Epidemiological data from 91 chronically infected patients (45 women and 46 men) were collected prospectively. Sera were tested for anti-HBc IgG, HBeAg, anti-HBe antibody and liver enzymes. Restriction Fragment Length Polymorphism (RFLP) analysis was confirmed by subsequent sequencing of the pre-S and S region of the viral genome in order to determine which HBV genotypes were prevalent among Moroccan patients. Results The mean age was 41 ± 12.4 years. Ten patients (11%) were positive for hepatitis B e antigen (HBeAg) and 81 (89%) were positive for anti-HBe antibodies. By the RLFP method, genotype D, pattern D2, was found in the 77 cases where HBV was successfully amplified. Phylogenetic analysis based on pre-S/S sequences revealed that genotype D in Morocco differed from others D strains subgenotypes (D1, D2, D3 and D4). In addition, the pre-core mutant defined as HBeAg-negative/anti-HBe-positive and HBV DNA positive was detected in 86% of cases. Conclusions Our results clearly show that genotype D and pre-core mutant are highly prevalent in Morocco.
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- 2008
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23. Complete genome sequence of two Christensenella minuta strains CIP 112228 and CIP 112229, isolated from human fecal samples.
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Bouchier C, Touak G, Rei D, and Clermont D
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Christensenella minuta is one of the representative bacterial species of the human gut microbiome. We report the complete genome sequence of two strains, Christensenella minuta CIP 112228 and CIP 112229, isolated from two healthy volunteers., Competing Interests: The authors declare no conflict of interest.
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- 2024
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24. Neisseria leonii sp. nov., isolated from the nose, lung, and liver of rabbits.
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Boutroux M, Favre-Rochex S, Gorgette O, Touak G, Mühle E, Bouchier C, Chesneau O, Veyrier FJ, Clermont D, and Rahi P
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- Animals, Rabbits, Fatty Acids analysis, Base Composition, RNA, Ribosomal, 16S genetics, Phylogeny, Neisseria isolation & purification, Neisseria classification, Neisseria genetics, DNA, Bacterial genetics, Bacterial Typing Techniques, Sequence Analysis, DNA, Liver microbiology, Lung microbiology
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A taxogenomic study of three strains (3986
T , 51.81, and JF 2415) isolated from rabbits between 1972 and 2000 led to the description of a new Neisseria species. The highest sequence similarity of the 16S rRNA gene was found to Neisseria animalis NCTC 10212T (96.7 %). The 16S rRNA gene similarity above 99 % and average nucleotide identity (ANI) values above 96 % among the strains, indicated that they belong to the same species. At the same time, the strains shared ANI values below 81 % and dDDH values below 24 % with all described Neisseria species. In the bac120 gene phylogenetic tree, the three strains clustered near Neisseria elongata and Neisseria bacilliformis in the Neisseria clade. However, the Neisseria clade is not monophyletic, and includes the type strains of Morococcus cerebrosus , Bergeriella denitrificans , Kingella potus , Uruburuella suis , and Uruburuella testudinis. Neisseria shayeganii clustered outside the clade with members of the genus Eikenella . Amino acid identity (AAI) values were calculated, and a threshold of 71 % was used to circumscribe the genus Neisseria . According to this proposed AAI threshold, strains 3986T , 51.81, and JF 2415 were placed within the genus Neisseria . The cells of the three strains were Gram-stain-negative diplococcobacilli and non-motile. Optimal growth on trypticase soy agar occurred at 37 °C and pH 8.5 in aerobic conditions. Notably, all strains exhibited indole production in the API-NH test, which is atypical for Neisseria and the family Neisseriaceae . The strains exhibited a common set of 68 peaks in their MALDI-TOF MS profiles, facilitating the swift and accurate identification of this species. Based on genotypic and phenotypic data, it is proposed that strains 3986T , 51.81, and JF 2415 represent a novel species within the genus Neisseria , for which the name Neisseria leonii sp. nov. is proposed (type strain 3986T =R726T =CIP 109994T =LMG 32907T ).- Published
- 2024
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25. Comparative Genomics of Synechococcus elongatus Explains the Phenotypic Diversity of the Strains.
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Adomako M, Ernst D, Simkovsky R, Chao YY, Wang J, Fang M, Bouchier C, Lopez-Igual R, Mazel D, Gugger M, and Golden SS
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- Bacterial Proteins genetics, Bacterial Proteins metabolism, Genomics, Phenotype, Photosynthesis, Synechococcus metabolism
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Strains of the freshwater cyanobacterium Synechococcus elongatus were first isolated approximately 60 years ago, and PCC 7942 is well established as a model for photosynthesis, circadian biology, and biotechnology research. The recent isolation of UTEX 3055 and subsequent discoveries in biofilm and phototaxis phenotypes suggest that lab strains of S. elongatus are highly domesticated. We performed a comprehensive genome comparison among the available genomes of S. elongatus and sequenced two additional laboratory strains to trace the loss of native phenotypes from the standard lab strains and determine the genetic basis of useful phenotypes. The genome comparison analysis provides a pangenome description of S. elongatus, as well as correction of extensive errors in the published sequence for the type strain PCC 6301. The comparison of gene sets and single nucleotide polymorphisms (SNPs) among strains clarifies strain isolation histories and, together with large-scale genome differences, supports a hypothesis of laboratory domestication. Prophage genes in laboratory strains, but not UTEX 3055, affect pigmentation, while unique genes in UTEX 3055 are necessary for phototaxis. The genomic differences identified in this study include previously reported SNPs that are, in reality, sequencing errors, as well as SNPs and genome differences that have phenotypic consequences. One SNP in the circadian response regulator rpaA that has caused confusion is clarified here as belonging to an aberrant clone of PCC 7942, used for the published genome sequence, that has confounded the interpretation of circadian fitness research. IMPORTANCE Synechococcus elongatus is a versatile and robust model cyanobacterium for photosynthetic metabolism and circadian biology research, with utility as a biological production platform. We compared the genomes of closely related S. elongatus strains to create a pangenome annotation to aid gene discovery for novel phenotypes. The comparative genomic analysis revealed the need for a new sequence of the species type strain PCC 6301 and includes two new sequences for S. elongatus strains PCC 6311 and PCC 7943. The genomic comparison revealed a pattern of early laboratory domestication of strains, clarifies the relationship between the strains PCC 6301 and UTEX 2973, and showed that differences in large prophage regions, operons, and even single nucleotides have effects on phenotypes as wide-ranging as pigmentation, phototaxis, and circadian gene expression.
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- 2022
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26. The virome of Rhipicephalus, Dermacentor and Haemaphysalis ticks from Eastern Romania includes novel viruses with potential relevance for public health.
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Bratuleanu BE, Temmam S, Chrétien D, Regnault B, Pérot P, Bouchier C, Bigot T, Savuța G, and Eloit M
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- Animals, Humans, Mammals, Phylogeny, Public Health, Romania epidemiology, Virome, Dermacentor, Ixodidae, RNA Viruses, Rhipicephalus, Viruses
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Ticks are involved in the transmission of various pathogens and several tick-borne diseases cause significant problems for the health of humans and livestock. The composition of viral communities in ticks and their interactions with pathogens, is poorly understood, particularly in Eastern Europe, an area that represents a major hub for animal-arthropod vectors exchanges (e.g., via bird migrations). The aim of this study was to describe the virome of Dermacentor sp., Rhipicephalus sp. and Haemaphysalis sp. ticks collected from relatively little studied regions of Romania (Iasi and Tulcea counties) located at the intersection of various biotopes, countries and routes of migrations. We also focused the study on viruses that could potentially have relevance for human and animal health. In 2019, more than 500 ticks were collected from the vegetation and from small ruminants and analysed by high-throughput transcriptome sequencing. Among the viral communities infecting Romanian ticks, viruses belonging to the Flaviviridae, Phenuiviridae and Nairoviridae families were identified and full genomes were derived. Phylogenetic analyses placed them in clades where mammalian isolates are found, suggesting that these viruses could constitute novel arboviruses. The characterization of these communities increase the knowledge of the diversity of viruses in Eastern Europe and provides a basis for further studies about the interrelationship between ticks and tick-borne viruses., (© 2021 Wiley-VCH GmbH.)
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- 2022
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27. Low CCR5 expression protects HIV-specific CD4+ T cells of elite controllers from viral entry.
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Claireaux M, Robinot R, Kervevan J, Patgaonkar M, Staropoli I, Brelot A, Nouël A, Gellenoncourt S, Tang X, Héry M, Volant S, Perthame E, Avettand-Fenoël V, Buchrieser J, Cokelaer T, Bouchier C, Ma L, Boufassa F, Hendou S, Libri V, Hasan M, Zucman D, de Truchis P, Schwartz O, Lambotte O, and Chakrabarti LA
- Subjects
- Chemokines, Down-Regulation, Gene Expression Regulation, Gene Products, gag metabolism, HIV Infections virology, Histocompatibility Antigens Class II, Humans, Mutation, Receptors, CCR5 genetics, Receptors, CXCR3, CD4-Positive T-Lymphocytes immunology, Elite Controllers, HIV Infections immunology, HIV-1 immunology, Receptors, CCR5 metabolism, Virus Internalization
- Abstract
HIV elite controllers maintain a population of CD4 + T cells endowed with high avidity for Gag antigens and potent effector functions. How these HIV-specific cells avoid infection and depletion upon encounter with the virus remains incompletely understood. Ex vivo characterization of single Gag-specific CD4 + T cells reveals an advanced Th1 differentiation pattern in controllers, except for the CCR5 marker, which is downregulated compared to specific cells of treated patients. Accordingly, controller specific CD4 + T cells show decreased susceptibility to CCR5-dependent HIV entry. Two controllers carried biallelic mutations impairing CCR5 surface expression, indicating that in rare cases CCR5 downregulation can have a direct genetic cause. Increased expression of β-chemokine ligands upon high-avidity antigen/TCR interactions contributes to autocrine CCR5 downregulation in controllers without CCR5 mutations. These findings suggest that genetic and functional regulation of the primary HIV coreceptor CCR5 play a key role in promoting natural HIV control., (© 2022. The Author(s).)
- Published
- 2022
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28. The Influence of Habitat on Viral Diversity in Neotropical Rodent Hosts.
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Tirera S, de Thoisy B, Donato D, Bouchier C, Lacoste V, Franc A, and Lavergne A
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- Animals, Ecology, Forests, Metagenome, Phylogeny, Zoonoses transmission, Ecosystem, Genetic Variation, Rodentia virology, Viruses classification, Viruses genetics, Zoonoses virology
- Abstract
Rodents are important reservoirs of numerous viruses, some of which have significant impacts on public health. Ecosystem disturbances and decreased host species richness have been associated with the emergence of zoonotic diseases. In this study, we aimed at (a) characterizing the viral diversity in seven neotropical rodent species living in four types of habitats and (b) exploring how the extent of environmental disturbance influences this diversity. Through a metagenomic approach, we identified 77,767 viral sequences from spleen, kidney, and serum samples. These viral sequences were attributed to 27 viral families known to infect vertebrates, invertebrates, plants, and amoeba. Viral diversities were greater in pristine habitats compared with disturbed ones, and lowest in peri-urban areas. High viral richness was observed in savannah areas. Differences in these diversities were explained by rare viruses that were generally more frequent in pristine forest and savannah habitats. Moreover, changes in the ecology and behavior of rodent hosts, in a given habitat, such as modifications to the diet in disturbed vs. pristine forests, are major determinants of viral composition. Lastly, the phylogenetic relationships of four vertebrate-related viral families ( Polyomaviridae , Flaviviridae , Togaviridae , and Phenuiviridae ) highlighted the wide diversity of these viral families, and in some cases, a potential risk of transmission to humans. All these findings provide significant insights into the diversity of rodent viruses in Amazonia, and emphasize that habitats and the host's dietary ecology may drive viral diversity. Linking viral richness and abundance to the ecology of their hosts and their responses to habitat disturbance could be the starting point for a better understanding of viral emergence and for future management of ecosystems.
- Published
- 2021
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29. Dynamics of extended-spectrum beta-lactamase-producing Enterobacterales colonization in long-term carriers following travel abroad.
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Armand-Lefèvre L, Rondinaud E, Desvillechabrol D, Mullaert J, Clermont O, Petitjean M, Ruppe E, Cokelaer T, Bouchier C, Tenaillon O, Ma L, Nooroya Y, Matheron S, The Voyag-R Study Group, Andremont A, Denamur E, and Kennedy SP
- Subjects
- Escherichia coli classification, Escherichia coli pathogenicity, Gastrointestinal Microbiome genetics, Genome, Bacterial genetics, High-Throughput Nucleotide Sequencing, Humans, Interspersed Repetitive Sequences genetics, Polymorphism, Single Nucleotide genetics, Whole Genome Sequencing, Carrier State epidemiology, Drug Resistance, Multiple, Bacterial genetics, Escherichia coli drug effects, Escherichia coli genetics, Travel, beta-Lactamases genetics
- Abstract
Travel to tropical regions is associated with high risk of acquiring extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) that are typically cleared in less than 3 months following return. The conditions leading to persistent carriage that exceeds 3 months in some travellers require investigation. Whole-genome sequencing (Illumina MiSeq) was performed on the 82 ESBL-E isolates detected upon return and 1, 2, 3, 6 and 12 months later from the stools of 11 long-term (>3 months) ESBL-E carriers following travel abroad. One to five different ESBL Escherichia coli strains were detected per traveller upon return, and this diminished to one after 3 months. Long-term carriage was due to the presence of the same ESBL E. coli strain, for more than 3 months, in 9 out of 11 travellers, belonging to epidemic sequence type complexes (STc 10, 14, 38, 69, 131 and 648). The mean carriage duration of strains belonging to phylogroups B2/D/F, associated with extra-intestinal virulence, was higher than that for commensal-associated A/B1/E phylogroups (3.5 vs 0.5 months, P =0.021). Genes encoding iron capture systems ( fyuA, irp ), toxins ( senB , sat ), adhesins ( flu, daaF, afa/nfaE , pap , ecpA ) and colicin ( cjrA ) were more often present in persistent strains than in transient ones. Single-nucleotide polymorphism (SNP) analysis in persistent strains showed a maximum divergence of eight SNPs over 12 months without signs of adaptation. Genomic plasticity was observed during the follow-up with the loss or gain of mobile genetic elements such as plasmids, integrons and/or transposons that may contain resistance genes at different points in the follow-up. Long-term colonization of ESBL-E following travel is primarily due to the acquisition of E. coli strains belonging to epidemic clones and harbouring 'virulence genes', allowing good adaptation to the intestinal microbiota.
- Published
- 2021
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30. Pathogenomic analyses of Mycobacterium microti, an ESX-1-deleted member of the Mycobacterium tuberculosis complex causing disease in various hosts.
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Orgeur M, Frigui W, Pawlik A, Clark S, Williams A, Ates LS, Ma L, Bouchier C, Parkhill J, Brodin P, and Brosch R
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- Animals, Arvicolinae microbiology, Bacterial Vaccines genetics, Disease Models, Animal, Guinea Pigs, High-Throughput Nucleotide Sequencing, Humans, Mice, Mice, SCID, Mycobacterium tuberculosis genetics, Phylogeny, Antigens, Bacterial genetics, Bacterial Proteins genetics, Bacterial Vaccines administration & dosage, Gene Deletion, Mycobacterium tuberculosis classification, Mycobacterium tuberculosis pathogenicity, Tuberculosis prevention & control, Whole Genome Sequencing methods
- Abstract
Mycobacterium microti is an animal-adapted member of the Mycobacterium tuberculosis complex (MTBC), which was originally isolated from voles, but has more recently also been isolated from other selected mammalian hosts, including occasionally from humans. Here, we have generated and analysed the complete genome sequences of five representative vole and clinical M. microti isolates using PacBio- and Illumina-based technologies, and have tested their virulence and vaccine potential in SCID (severe combined immune deficient) mouse and/or guinea pig infection models. We show that the clinical isolates studied here cluster separately in the phylogenetic tree from vole isolates and other clades from publicly available M. microti genome sequences. These data also confirm that the vole and clinical M. microti isolates were all lacking the specific RD1
mic region, which in other tubercle bacilli encodes the ESX-1 type VII secretion system. Biochemical analysis further revealed marked phenotypic differences between isolates in type VII-mediated secretion of selected PE and PPE proteins, which in part were attributed to specific genetic polymorphisms. Infection experiments in the highly susceptible SCID mouse model showed that the clinical isolates were significantly more virulent than the tested vole isolates, but still much less virulent than the M. tuberculosis H37Rv control strain. The strong attenuation of the ATCC 35872 vole isolate in immunocompromised mice, even compared to the attenuated BCG (bacillus Calmette-Guérin) vaccine, and its historic use in human vaccine trials encouraged us to test this strain's vaccine potential in a guinea pig model, where it demonstrated similar protective efficacy as a BCG control, making it a strong candidate for vaccination of immunocompromised individuals in whom BCG vaccination is contra-indicated. Overall, we provide new insights into the genomic and phenotypic variabilities and particularities of members of an understudied clade of the MTBC, which all share a recent common ancestor that is characterized by the deletion of the RD1mic region.- Published
- 2021
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31. A Second Genome Sequence of an Enterovirus C99 Detected in a Healthy Chimpanzee.
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Mombo IM, Boundenga L, Berthet N, Atencia R, Cox D, Maganga GD, Bouchier C, Leroy EM, and Rougeron V
- Abstract
We report the nearly complete genome sequence of an enterovirus 99 strain (Cpz-IJC08) detected in a healthy chimpanzee from the Tchimpounga Sanctuary in the Republic of Congo. According to the phylogeny, Cpz-IJC08 clustered with Cpz-IJC04, a previously identified chimpanzee enterovirus from the same sanctuary, isolated from an animal with signs of acute flaccid paralysis., (Copyright © 2020 Mombo et al.)
- Published
- 2020
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32. TbD1 deletion as a driver of the evolutionary success of modern epidemic Mycobacterium tuberculosis lineages.
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Bottai D, Frigui W, Sayes F, Di Luca M, Spadoni D, Pawlik A, Zoppo M, Orgeur M, Khanna V, Hardy D, Mangenot S, Barbe V, Medigue C, Ma L, Bouchier C, Tavanti A, Larrouy-Maumus G, and Brosch R
- Subjects
- Animals, Guinea Pigs, Humans, Mice, Mice, Inbred C3H, Mycobacterium tuberculosis classification, Mycobacterium tuberculosis pathogenicity, Phylogeny, Sequence Deletion, Virulence, Evolution, Molecular, Mycobacterium tuberculosis genetics, Tuberculosis microbiology
- Abstract
Mycobacterium tuberculosis (Mtb) strains are classified into different phylogenetic lineages (L), three of which (L2/L3/L4) emerged from a common progenitor after the loss of the MmpS6/MmpL6-encoding Mtb-specific deletion 1 region (TbD1). These TbD1-deleted "modern" lineages are responsible for globally-spread tuberculosis epidemics, whereas TbD1-intact "ancestral" lineages tend to be restricted to specific geographical areas, such as South India and South East Asia (L1) or East Africa (L7). By constructing and characterizing a panel of recombinant TbD1-knock-in and knock-out strains and comparison with clinical isolates, here we show that deletion of TbD1 confers to Mtb a significant increase in resistance to oxidative stress and hypoxia, which correlates with enhanced virulence in selected cellular, guinea pig and C3HeB/FeJ mouse infection models, the latter two mirroring in part the development of hypoxic granulomas in human disease progression. Our results suggest that loss of TbD1 at the origin of the L2/L3/L4 Mtb lineages was a key driver for their global epidemic spread and outstanding evolutionary success.
- Published
- 2020
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33. Author Correction: The population structure of Clostridium tetani deduced from its pan-genome.
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Chapeton-Montes D, Plourde L, Bouchier C, Ma L, Diancourt L, Criscuolo A, Popoff MR, and Brüggemann H
- Abstract
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
- Published
- 2019
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34. A simple, reproducible and cost-effective procedure to analyse gut phageome: from phage isolation to bioinformatic approach.
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d'Humières C, Touchon M, Dion S, Cury J, Ghozlane A, Garcia-Garcera M, Bouchier C, Ma L, Denamur E, and P C Rocha E
- Subjects
- Bacteriophages isolation & purification, Computational Biology, Cost-Benefit Analysis, Feces, Genome, Viral, Humans, Metagenomics, Microbiota genetics, Bacteriophages genetics, Intestines virology, Metagenome genetics, Phylogeny
- Abstract
The microbiota of the human gut is a complex and rich community where bacteria and their viruses, the bacteriophages, are dominant. There are few studies on the phage community and no clear standard for isolating them, sequencing and analysing their genomes. Since this makes comparisons between studies difficult, we aimed at defining an easy, low-cost, and reproducible methodology. We analysed five different techniques to isolate phages from human adult faeces and developed an approach to analyse their genomes in order to quantify contamination and classify phage contigs in terms of taxonomy and lifestyle. We chose the polyethylene glycol concentration method to isolate phages because of its simplicity, low cost, reproducibility, and of the high number and diversity of phage sequences that we obtained. We also tested the reproducibility of this method with multiple displacement amplification (MDA) and showed that MDA severely decreases the phage genetic diversity of the samples and the reproducibility of the method. Lastly, we studied the influence of sequencing depth on the analysis of phage diversity and observed the beginning of a plateau for phage contigs at 20,000,000 reads. This work contributes to the development of methods for the isolation of phages in faeces and for their comparative analysis.
- Published
- 2019
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35. The population structure of Clostridium tetani deduced from its pan-genome.
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Chapeton-Montes D, Plourde L, Bouchier C, Ma L, Diancourt L, Criscuolo A, Popoff MR, and Brüggemann H
- Subjects
- Clostridium tetani pathogenicity, Collagenases genetics, Conserved Sequence, Neurotoxins genetics, Phylogeny, Species Specificity, Tetanus Toxin genetics, Virulence Factors genetics, Clostridium tetani genetics, Genome, Bacterial genetics
- Abstract
Clostridium tetani produces a potent neurotoxin, the tetanus neurotoxin (TeNT) that is responsible for the worldwide neurological disease tetanus, but which can be efficiently prevented by vaccination with tetanus toxoid. Until now only one type of TeNT has been characterized and very little information exists about the heterogeneity among C. tetani strains. We report here the genome sequences of 26 C. tetani strains, isolated between 1949 and 2017 and obtained from different locations. Genome analyses revealed that the C. tetani population is distributed in two phylogenetic clades, a major and a minor one, with no evidence for clade separation based on geographical origin or time of isolation. The chromosome of C. tetani is highly conserved; in contrast, the TeNT-encoding plasmid shows substantial heterogeneity. TeNT itself is highly conserved among all strains; the most relevant difference is an insertion of four amino acids in the C-terminal receptor-binding domain in four strains that might impact on receptor-binding properties. Other putative virulence factors, including tetanolysin and collagenase, are encoded in all genomes. This study highlights the population structure of C. tetani and suggests that tetanus-causing strains did not undergo extensive evolutionary diversification, as judged from the high conservation of its main virulence factors.
- Published
- 2019
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36. Comparison of intra- and inter-host genetic diversity in rabies virus during experimental cross-species transmission.
- Author
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Bonnaud EM, Troupin C, Dacheux L, Holmes EC, Monchatre-Leroy E, Tanguy M, Bouchier C, Cliquet F, Barrat J, and Bourhy H
- Subjects
- Animals, Cell Line, Dogs, Female, Foxes genetics, Foxes immunology, Foxes virology, High-Throughput Nucleotide Sequencing, Host-Parasite Interactions genetics, Male, Mutation, Dog Diseases genetics, Dog Diseases immunology, Evolution, Molecular, Host-Parasite Interactions immunology, Rabies genetics, Rabies immunology, Rabies virus physiology
- Abstract
The development of high-throughput genome sequencing enables accurate measurements of levels of sub-consensus intra-host virus genetic diversity and analysis of the role played by natural selection during cross-species transmission. We analysed the natural and experimental evolution of rabies virus (RABV), an important example of a virus that is able to make multiple host jumps. In particular, we (i) analyzed RABV evolution during experimental host switching with the goal of identifying possible genetic markers of host adaptation, (ii) compared the mutational changes observed during passage with those observed in natura, and (iii) determined whether the colonization of new hosts or tissues requires adaptive evolution in the virus. To address these aims, animal infection models (dog and fox) and primary cell culture models (embryo brain cells of dog and fox) were developed and viral variation was studied in detail through deep genome sequencing. Our analysis revealed a strong unidirectional host evolutionary effect, as dog-adapted rabies virus was able to replicate in fox and fox cells relatively easily, while dogs or neuronal dog cells were not easily susceptible to fox adapted-RABV. This suggests that dog RABV may be able to adapt to some hosts more easily than other host variants, or that when RABV switched from dogs to red foxes it lost its ability to adapt easily to other species. Although no difference in patterns of mutation variation between different host organs was observed, mutations were common following both in vitro and in vivo passage. However, only a small number of these mutations also appeared in natura, suggesting that adaptation during successful cross-species virus transmission is a complex, multifactorial evolutionary process., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2019
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37. Publisher Correction: Genomic insights into the 2016-2017 cholera epidemic in Yemen.
- Author
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Weill FX, Domman D, Njamkepo E, Almesbahi AA, Naji M, Nasher SS, Rakesh A, Assiri AM, Sharma NC, Kariuki S, Pourshafie MR, Rauzier J, Abubakar A, Carter JY, Wamala JF, Seguin C, Bouchier C, Malliavin T, Bakhshi B, Abulmaali HHN, Kumar D, Njoroge SM, Malik MR, Kiiru J, Luquero FJ, Azman AS, Ramamurthy T, Thomson NR, and Quilici ML
- Abstract
In the HTML version of this Letter, the affiliations for authors Andrew S. Azman, Dhirendra Kumar and Thandavarayan Ramamurthy were inverted (the PDF and print versions of the Letter were correct); the affiliations have been corrected online.
- Published
- 2019
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38. Genomic insights into the 2016-2017 cholera epidemic in Yemen.
- Author
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Weill FX, Domman D, Njamkepo E, Almesbahi AA, Naji M, Nasher SS, Rakesh A, Assiri AM, Sharma NC, Kariuki S, Pourshafie MR, Rauzier J, Abubakar A, Carter JY, Wamala JF, Seguin C, Bouchier C, Malliavin T, Bakhshi B, Abulmaali HHN, Kumar D, Njoroge SM, Malik MR, Kiiru J, Luquero FJ, Azman AS, Ramamurthy T, Thomson NR, and Quilici ML
- Subjects
- Humans, Phylogeny, Vibrio cholerae classification, Yemen epidemiology, Cholera epidemiology, Cholera microbiology, Genome, Bacterial genetics, Genomics, Vibrio cholerae genetics, Vibrio cholerae isolation & purification
- Abstract
Yemen is currently experiencing, to our knowledge, the largest cholera epidemic in recent history. The first cases were declared in September 2016, and over 1.1 million cases and 2,300 deaths have since been reported
1 . Here we investigate the phylogenetic relationships, pathogenesis and determinants of antimicrobial resistance by sequencing the genomes of Vibrio cholerae isolates from the epidemic in Yemen and recent isolates from neighbouring regions. These 116 genomic sequences were placed within the phylogenetic context of a global collection of 1,087 isolates of the seventh pandemic V. cholerae serogroups O1 and O139 biotype El Tor2-4 . We show that the isolates from Yemen that were collected during the two epidemiological waves of the epidemic1 -the first between 28 September 2016 and 23 April 2017 (25,839 suspected cases) and the second beginning on 24 April 2017 (more than 1 million suspected cases)-are V. cholerae serotype Ogawa isolates from a single sublineage of the seventh pandemic V. cholerae O1 El Tor (7PET) lineage. Using genomic approaches, we link the epidemic in Yemen to global radiations of pandemic V. cholerae and show that this sublineage originated from South Asia and that it caused outbreaks in East Africa before appearing in Yemen. Furthermore, we show that the isolates from Yemen are susceptible to several antibiotics that are commonly used to treat cholera and to polymyxin B, resistance to which is used as a marker of the El Tor biotype.- Published
- 2019
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39. Sequana coverage: detection and characterization of genomic variations using running median and mixture models.
- Author
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Desvillechabrol D, Bouchier C, Kennedy S, and Cokelaer T
- Subjects
- Bacteria genetics, DNA Copy Number Variations, Fungi genetics, Genetic Variation, High-Throughput Nucleotide Sequencing, Viruses genetics, Algorithms, Genome
- Abstract
Background: In addition to mapping quality information, the Genome coverage contains valuable biological information such as the presence of repetitive regions, deleted genes, or copy number variations (CNVs). It is essential to take into consideration atypical regions, trends (e.g., origin of replication), or known and unknown biases that influence coverage. It is also important that reported events have robust statistics (e.g. z-score) associated with their detections as well as precise location., Results: We provide a stand-alone application, sequana_coverage, that reports genomic regions of interest (ROIs) that are significantly over- or underrepresented in high-throughput sequencing data. Significance is associated with the events as well as characteristics such as length of the regions. The algorithm first detrends the data using an efficient running median algorithm. It then estimates the distribution of the normalized genome coverage with a Gaussian mixture model. Finally, a z-score statistic is assigned to each base position and used to separate the central distribution from the ROIs (i.e., under- and overcovered regions). A double thresholds mechanism is used to cluster the genomic ROIs. HTML reports provide a summary with interactive visual representations of the genomic ROIs with standard plots and metrics. Genomic variations such as single-nucleotide variants or CNVs can be effectively identified at the same time.
- Published
- 2018
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40. Erratum: Generating genomic platforms to study Candida albicans pathogenesis.
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Legrand M, Bachellier-Bassi S, Lee KK, Chaudhari Y, Tournu H, Arbogast L, Boyer H, Chauvel M, Cabral V, Maufrais C, Nesseir A, Maslanka I, Permal E, Rossignol T, Walker LA, Zeidler U, Znaidi S, Schoeters F, Majgier C, Julien RA, Ma L, Tichit M, Bouchier C, Van Dijck P, Munro CA, and d'Enfert C
- Published
- 2018
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41. Generating genomic platforms to study Candida albicans pathogenesis.
- Author
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Legrand M, Bachellier-Bassi S, Lee KK, Chaudhari Y, Tournu H, Arbogast L, Boyer H, Chauvel M, Cabral V, Maufrais C, Nesseir A, Maslanka I, Permal E, Rossignol T, Walker LA, Zeidler U, Znaidi S, Schoeters F, Majgier C, Julien RA, Ma L, Tichit M, Bouchier C, Van Dijck P, Munro CA, and d'Enfert C
- Subjects
- Candida albicans pathogenicity, Databases, Nucleic Acid, Genetic Vectors, Genomics, Protein Interaction Mapping, Candida albicans genetics, Open Reading Frames
- Abstract
The advent of the genomic era has made elucidating gene function on a large scale a pressing challenge. ORFeome collections, whereby almost all ORFs of a given species are cloned and can be subsequently leveraged in multiple functional genomic approaches, represent valuable resources toward this endeavor. Here we provide novel, genome-scale tools for the study of Candida albicans, a commensal yeast that is also responsible for frequent superficial and disseminated infections in humans. We have generated an ORFeome collection composed of 5099 ORFs cloned in a Gateway™ donor vector, representing 83% of the currently annotated coding sequences of C. albicans. Sequencing data of the cloned ORFs are available in the CandidaOrfDB database at http://candidaorfeome.eu. We also engineered 49 expression vectors with a choice of promoters, tags and selection markers and demonstrated their applicability to the study of target ORFs transferred from the C. albicans ORFeome. In addition, the use of the ORFeome in the detection of protein-protein interaction was demonstrated. Mating-compatible strains as well as Gateway™-compatible two-hybrid vectors were engineered, validated and used in a proof of concept experiment. These unique and valuable resources should greatly facilitate future functional studies in C. albicans and the elucidation of mechanisms that underlie its pathogenicity.
- Published
- 2018
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42. Unexpected Genomic and Phenotypic Diversity of Mycobacterium africanum Lineage 5 Affects Drug Resistance, Protein Secretion, and Immunogenicity.
- Author
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Ates LS, Dippenaar A, Sayes F, Pawlik A, Bouchier C, Ma L, Warren RM, Sougakoff W, Majlessi L, van Heijst JWJ, Brossier F, and Brosch R
- Subjects
- Adult, Animals, Base Pairing genetics, Computational Biology, Drug Resistance, Bacterial drug effects, Female, Genetic Markers, Genotype, Humans, Isoniazid pharmacology, Male, Mice, Inbred C57BL, Middle Aged, Mycobacterium drug effects, Mycobacterium isolation & purification, Phenotype, Sequence Deletion genetics, T-Lymphocytes drug effects, T-Lymphocytes immunology, Bacterial Proteins metabolism, Drug Resistance, Bacterial genetics, Genomics, Mycobacterium genetics, Mycobacterium immunology, Phylogeny
- Abstract
Mycobacterium africanum consists of Lineages L5 and L6 of the Mycobacterium tuberculosis complex (MTBC) and causes human tuberculosis in specific regions of Western Africa, but is generally not transmitted in other parts of the world. Since M. africanum is evolutionarily closely placed between the globally dispersed Mycobacterium tuberculosis and animal-adapted MTBC-members, these lineages provide valuable insight into M. tuberculosis evolution. Here, we have collected 15 M. africanum L5 strains isolated in France over 4 decades. Illumina sequencing and phylogenomic analysis revealed a previously underappreciated diversity within L5, which consists of distinct sublineages. L5 strains caused relatively high levels of extrapulmonary tuberculosis and included multi- and extensively drug-resistant isolates, especially in the newly defined sublineage L5.2. The specific L5 sublineages also exhibit distinct phenotypic characteristics related to in vitro growth, protein secretion and in vivo immunogenicity. In particular, we identified a PE_PGRS and PPE-MPTR secretion defect specific for sublineage L5.2, which was independent of PPE38. Furthermore, L5 isolates were able to efficiently secrete and induce immune responses against ESX-1 substrates contrary to previous predictions. These phenotypes of Type VII protein secretion and immunogenicity provide valuable information to better link genome sequences to phenotypic traits and thereby understand the evolution of the MTBC.
- Published
- 2018
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43. A novel species of the marine cyanobacterium Acaryochloris with a unique pigment content and lifestyle.
- Author
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Partensky F, Six C, Ratin M, Garczarek L, Vaulot D, Probert I, Calteau A, Gourvil P, Marie D, Grébert T, Bouchier C, Le Panse S, Gachenot M, Rodríguez F, and Garrido JL
- Subjects
- Chlorophyll metabolism, Chlorophyll A metabolism, Cyanobacteria classification, Cyanobacteria metabolism, Phytoplankton classification, Phytoplankton metabolism
- Abstract
All characterized members of the ubiquitous genus Acaryochloris share the unique property of containing large amounts of chlorophyll (Chl) d, a pigment exhibiting a red absorption maximum strongly shifted towards infrared compared to Chl a. Chl d is the major pigment in these organisms and is notably bound to antenna proteins structurally similar to those of Prochloron, Prochlorothrix and Prochlorococcus, the only three cyanobacteria known so far to contain mono- or divinyl-Chl a and b as major pigments and to lack phycobilisomes. Here, we describe RCC1774, a strain isolated from the foreshore near Roscoff (France). It is phylogenetically related to members of the Acaryochloris genus but completely lacks Chl d. Instead, it possesses monovinyl-Chl a and b at a b/a molar ratio of 0.16, similar to that in Prochloron and Prochlorothrix. It differs from the latter by the presence of phycocyanin and a vestigial allophycocyanin energetically coupled to photosystems. Genome sequencing confirmed the presence of phycobiliprotein and Chl b synthesis genes. Based on its phylogeny, ultrastructural characteristics and unique pigment suite, we describe RCC1774 as a novel species that we name Acaryochloris thomasi. Its very unusual pigment content compared to other Acaryochloris spp. is likely related to its specific lifestyle.
- Published
- 2018
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44. Gene flow contributes to diversification of the major fungal pathogen Candida albicans.
- Author
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Ropars J, Maufrais C, Diogo D, Marcet-Houben M, Perin A, Sertour N, Mosca K, Permal E, Laval G, Bouchier C, Ma L, Schwartz K, Voelz K, May RC, Poulain J, Battail C, Wincker P, Borman AM, Chowdhary A, Fan S, Kim SH, Le Pape P, Romeo O, Shin JH, Gabaldon T, Sherlock G, Bougnoux ME, and d'Enfert C
- Subjects
- Candida albicans classification, Candida albicans pathogenicity, Candidiasis microbiology, Gene Frequency, Humans, Linkage Disequilibrium, Loss of Heterozygosity, Phylogeny, Polymorphism, Single Nucleotide, Species Specificity, Virulence genetics, Whole Genome Sequencing, Candida albicans genetics, Gene Flow, Genes, Fungal genetics, Genetic Variation
- Abstract
Elucidating population structure and levels of genetic diversity and recombination is necessary to understand the evolution and adaptation of species. Candida albicans is the second most frequent agent of human fungal infections worldwide, causing high-mortality rates. Here we present the genomic sequences of 182 C. albicans isolates collected worldwide, including commensal isolates, as well as ones responsible for superficial and invasive infections, constituting the largest dataset to date for this major fungal pathogen. Although, C. albicans shows a predominantly clonal population structure, we find evidence of gene flow between previously known and newly identified genetic clusters, supporting the occurrence of (para)sexuality in nature. A highly clonal lineage, which experimentally shows reduced fitness, has undergone pseudogenization in genes required for virulence and morphogenesis, which may explain its niche restriction. Candida albicans thus takes advantage of both clonality and gene flow to diversify.
- Published
- 2018
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45. Sequanix: a dynamic graphical interface for Snakemake workflows.
- Author
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Desvillechabrol D, Legendre R, Rioualen C, Bouchier C, van Helden J, Kennedy S, and Cokelaer T
- Subjects
- Computational Biology methods, Data Visualization, Software
- Abstract
Summary: We designed a PyQt graphical user interface-Sequanix-aimed at democratizing the use of Snakemake pipelines in the NGS space and beyond. By default, Sequanix includes Sequana NGS pipelines (Snakemake format) (http://sequana.readthedocs.io), and is also capable of loading any external Snakemake pipeline. New users can easily, visually, edit configuration files of expert-validated pipelines and can interactively execute these production-ready workflows. Sequanix will be useful to both Snakemake developers in exposing their pipelines and to a wide audience of users., Availability and Implementation: Source on http://github.com/sequana/sequana, bio-containers on http://bioconda.github.io and Singularity hub (http://singularity-hub.org)., Contact: dimitri.desvillechabrol@pasteur.fr or thomas.cokelaer@pasteur.fr., Supplementary Information: Supplementary data are available at Bioinformatics online.
- Published
- 2018
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46. Short genome report of cellulose-producing commensal Escherichia coli 1094.
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Bernal-Bayard J, Gomez-Valero L, Wessel A, Khanna V, Bouchier C, and Ghigo JM
- Abstract
Bacterial surface colonization and biofilm formation often rely on the production of an extracellular polymeric matrix that mediates cell-cell and cell-surface contacts. In Escherichia coli and many Betaproteobacteria and Gammaproteobacteria cellulose is often the main component of the extracellular matrix. Here we report the complete genome sequence of the cellulose producing strain E. coli 1094 and compare it with five other closely related genomes within E. coli phylogenetic group A. We present a comparative analysis of the regions encoding genes responsible for cellulose biosynthesis and discuss the changes that could have led to the loss of this important adaptive advantage in several E. coli strains. Data deposition: The annotated genome sequence has been deposited at the European Nucleotide Archive under the accession number PRJEB21000., Competing Interests: The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
- Published
- 2018
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47. Diverse laboratory colonies of Aedes aegypti harbor the same adult midgut bacterial microbiome.
- Author
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Dickson LB, Ghozlane A, Volant S, Bouchier C, Ma L, Vega-Rúa A, Dusfour I, Jiolle D, Paupy C, Mayanja MN, Kohl A, Lutwama JJ, Duong V, and Lambrechts L
- Subjects
- Animals, Cluster Analysis, DNA, Ribosomal chemistry, DNA, Ribosomal genetics, Gastrointestinal Tract microbiology, Metagenomics, Phylogeny, RNA, Ribosomal, 16S genetics, Sequence Analysis, DNA, Aedes microbiology, Bacteria classification, Bacteria genetics, Gastrointestinal Microbiome
- Abstract
Background: Host-associated microbes, collectively known as the microbiota, play an important role in the biology of multicellular organisms. In mosquito vectors of human pathogens, the gut bacterial microbiota influences vectorial capacity and has become the subject of intense study. In laboratory studies of vector biology, genetic effects are often inferred from differences between geographically and genetically diverse colonies of mosquitoes that are reared in the same insectary. It is unclear, however, to what extent genetic effects can be confounded by uncontrolled differences in the microbiota composition among mosquito colonies. To address this question, we used 16S metagenomics to compare the midgut bacterial microbiome of six laboratory colonies of Aedes aegypti recently derived from wild populations representing the geographical range and genetic diversity of the species., Results: We found that the diversity, abundance, and community structure of the midgut bacterial microbiome was remarkably similar among the six different colonies of Ae. aegypti, regardless of their geographical origin. We also confirmed the relatively low complexity of bacterial communities inhabiting the mosquito midgut., Conclusions: Our finding that geographically diverse colonies of Ae. aegypti reared in the same insectary harbor a similar gut bacterial microbiome supports the conclusion that the gut microbiota of adult mosquitoes is environmentally determined regardless of the host genotype. Thus, uncontrolled differences in microbiota composition are unlikely to represent a significant confounding factor in genetic studies of vector biology.
- Published
- 2018
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48. Early transmissible ampicillin resistance in zoonotic Salmonella enterica serotype Typhimurium in the late 1950s: a retrospective, whole-genome sequencing study.
- Author
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Tran-Dien A, Le Hello S, Bouchier C, and Weill FX
- Subjects
- Ampicillin therapeutic use, Animals, Anti-Bacterial Agents therapeutic use, Disk Diffusion Antimicrobial Tests, France, Gene Transfer Techniques, Global Health, History, 20th Century, Humans, Retrospective Studies, Salmonella Infections history, Salmonella Infections, Animal history, Salmonella typhimurium classification, Salmonella typhimurium genetics, Salmonella typhimurium isolation & purification, Tunisia, United Kingdom, Whole Genome Sequencing, Ampicillin Resistance, Food Microbiology, Gene Transfer, Horizontal, Plasmids, Salmonella Infections microbiology, Salmonella Infections, Animal microbiology, Salmonella typhimurium drug effects
- Abstract
Background: Ampicillin, the first semi-synthetic penicillin active against Enterobacteriaceae, was released onto the market in 1961. The first outbreaks of disease caused by ampicillin-resistant strains of Salmonella enterica serotype Typhimurium were identified in the UK in 1962 and 1964. We aimed to date the emergence of this resistance in historical isolates of S enterica serotype Typhimurium., Methods: In this retrospective, whole-genome sequencing study, we analysed 288 S enterica serotype Typhimurium isolates collected between 1911 and 1969 from 31 countries on four continents and from various sources including human beings, animals, feed, and food. All isolates were tested for antimicrobial drug susceptibility with the disc diffusion method, and isolates shown to be resistant to ampicillin underwent resistance-transfer experiments. To provide insights into population structure and mechanisms of ampicillin resistance, we did whole-genome sequencing on a subset of 225 isolates, selected to maximise source, spatiotemporal, and genetic diversity., Findings: 11 (4%) of 288 isolates were resistant to ampicillin because of acquisition of various β lactamase genes, including bla
TEM-1 , carried by various plasmids, including the virulence plasmid of S enterica serotype Typhimurium. These 11 isolates were from three phylogenomic groups. One isolate producing TEM-1 β lactamase was isolated in France in 1959 and two isolates producing TEM-1 β lactamase were isolated in Tunisia in 1960, before ampicillin went on sale. The vectors for ampicillin resistance were different from those reported in the strains responsible for the outbreaks in the UK in the 1960s., Interpretation: The association between antibiotic use and selection of resistance determinants is not as direct as often presumed. Our results suggest that the non-clinical use of narrow-spectrum penicillins (eg, benzylpenicillin) might have favoured the diffusion of plasmids carrying the blaTEM-1 gene in S enterica serotype Typhimurium in the late 1950s., Funding: Institut Pasteur, Santé publique France, the French Government's Investissement d'Avenir programme, the Fondation Le Roch-Les Mousquetaires., (Copyright © 2018 Elsevier Ltd. All rights reserved.)- Published
- 2018
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49. Plasmid-mediated doxycycline resistance in a Yersinia pestis strain isolated from a rat.
- Author
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Cabanel N, Bouchier C, Rajerison M, and Carniel E
- Subjects
- Animals, DNA, Bacterial genetics, Disk Diffusion Antimicrobial Tests, Madagascar, Plague microbiology, Rats, Streptomycin pharmacology, Yersinia pestis isolation & purification, Anti-Bacterial Agents pharmacology, Doxycycline pharmacology, Drug Resistance, Multiple, Bacterial genetics, Plasmids genetics, Yersinia pestis drug effects, Yersinia pestis genetics
- Abstract
The emergence of antibiotic-resistant Yersinia pestis strains represents a public health concern. Two antibiotic-resistant Y. pestis strains isolated from Madagascar have been previously identified and characterised. Both strains carried conjugative plasmids that conferred resistance to streptomycin or to multiple antibacterial drugs, respectively. Here we characterised a novel Y. pestis strain (IP2180H) that exhibited resistance to doxycycline. This strain was isolated from a rat in Antananarivo (Madagascar) in 1998. Resistance was carried by a conjugative plasmid (pIP2180H) homologous to pB71 from Salmonella enterica. The plasmid of the previously identified streptomycin-resistant Y. pestis strain was also sequenced and it was found that the three antibiotic resistance Y. pestis plasmids sequenced until now are genetically unrelated and are also unrelated to multidrug resistance plasmids from the phylogenetically close bacterial species Yersinia pseudotuberculosis. The fact that the three antibiotic-resistant Malagasy Y. pestis strains were isolated from different hosts, at different times, from distant locations, and carried unrelated plasmids indicates independent horizontal acquisition of genetic material and further demonstrates the capacity of Y. pestis to acquire antibiotic resistance plasmids under natural conditions. Since these resistance plasmids can frequently carry or easily trap antibiotic resistance cassettes, the emergence of new multidrug-resistant Y. pestis strains may be expected and would represent a major health threat., (Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.)
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- 2018
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50. Integrated view of Vibrio cholerae in the Americas.
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Domman D, Quilici ML, Dorman MJ, Njamkepo E, Mutreja A, Mather AE, Delgado G, Morales-Espinosa R, Grimont PAD, Lizárraga-Partida ML, Bouchier C, Aanensen DM, Kuri-Morales P, Tarr CL, Dougan G, Parkhill J, Campos J, Cravioto A, Weill FX, and Thomson NR
- Subjects
- Cholera prevention & control, Communicable Disease Control, Drug Resistance, Multiple, Bacterial, Humans, Latin America epidemiology, Sequence Analysis, DNA, Vibrio cholerae isolation & purification, Cholera epidemiology, Cholera microbiology, Pandemics prevention & control, Vibrio cholerae classification, Vibrio cholerae genetics
- Abstract
Latin America has experienced two of the largest cholera epidemics in modern history; one in 1991 and the other in 2010. However, confusion still surrounds the relationships between globally circulating pandemic Vibrio cholerae clones and local bacterial populations. We used whole-genome sequencing to characterize cholera across the Americas over a 40-year time span. We found that both epidemics were the result of intercontinental introductions of seventh pandemic El Tor V. cholerae and that at least seven lineages local to the Americas are associated with disease that differs epidemiologically from epidemic cholera. Our results consolidate historical accounts of pandemic cholera with data to show the importance of local lineages, presenting an integrated view of cholera that is important to the design of future disease control strategies., (Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
- Published
- 2017
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