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6. Dual Control of Host Actin Polymerization by a Legionella Effector Pair.

Author

Pillon, M., Michard, C., Baïlo, N., Bougnon, J., Picq, K., Dubois, O., Andrea, C., Attaiech, L., Daubin, V., Jarraud, S., Kay, E., and Doublet, P.

Subjects
ACTIN, LEGIONELLA, LEGIONELLA pneumophila, BACTERIAL proteins, CYTOSKELETON
Abstract

Host actin cytoskeleton is often targeted by pathogenic bacteria through the secretion of effectors. Legionella pneumophila virulence relies on the injection of the largest known arsenal of bacterial proteins, over 300 Dot/Icm type 4 secretion system effectors, into the host cytosol. Here, we define the functional interactions between VipA and LegK2, two effectors with antagonistic activities towards actin polymerization that have been proposed to interfere with the endosomal pathway. We confirmed the prominent role of LegK2 effector in Legionella infection, as the deletion of legK2 results in defects in the inhibition of actin polymerization at the Legionella-containing vacuole, as well as in endosomal escape of bacteria and subsequent intracellular replication. More importantly, we observed the restoration of the ΔlegK2 mutant defects, upon deletion of vipA gene, making LegK2/VipA a novel example of effector-effector suppression pair that targets the actin cytoskeleton and whose functional interaction impacts L. pneumophila virulence. We demonstrated that LegK2 and VipA do not modulate each other's activity in a "metaeffector" relationship. Instead, the antagonistic activities of the LegK2/VipA effector pair would target different substrates, Arp2/3 for LegK2 and G-actin for VipA, to temporally control actin polymerization at the LCV and interfere with phagosome maturation and endosome recycling, thus contributing to the intracellular life cycle of the bacterium. Strikingly, the functional interaction between LegK2 and VipA is consolidated by an evolutionary history that has refined the best effector repertoire for the benefit of L. pneumophila virulence. [ABSTRACT FROM AUTHOR]

Published
2024
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14. Genetic Diversity of Legionella pneumophila

Author

Cazalet, C., primary, Jarraud, S., additional, Ghavi-Helm, Y., additional, Allignet, J., additional, Kunst, F., additional, Etienne, J., additional, Glaser, P., additional, and Buchrieser, C., additional

Published
2014
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19. Exfoliatin-producing strains define a fourth agr specificity group in Staphylococcus aureus

Author

Jarraud, S., Lyon, G.J., Figueiredo, A.M.S., Gerard, Lina, Vandenesch, F., Etienne, J., Muir, T.W., and Novick, R.P.

Subjects
Staphylococcus aureus -- Physiological aspects, Exotoxins -- Physiological aspects, Cladistic analysis -- Research, Biological sciences
Abstract

Research identifies a new group of Staphylococcus aureus exhibiting density-sensing agr system phenotype and its early activation in the exponential phase. Data further suggest that the new group includes most of the exfoliatin-producing strains.

Published
2000

30. Prediction of the origin of French Legionella pneumophila strains using a mixed-genome microarray

Author

Boer, J.W. den, Euser, S.M., Nagelkerke, N.J., Schuren, F., Jarraud, S., and Etienne, J.

Subjects
Micro-array, Biomedical Innovation, Environmental Exposure, Pneumonia, Negative Predictive Value, Genomotyping, Legionella Pneumophila, MSB - Microbiology and Systems Biology, Life, Virulence-associated Epitope, Random Forest Algorithm, Public Health, Legionnaires' Disease, EELS - Earth, Environmental and Life Sciences, Biology, Healthy Living
Abstract

Background: Legionella is a water and soil bacterium that can infect humans, causing a pneumonia known as Legionnaires' disease. The pneumonia is almost exclusively caused by the species L. pneumophila, of which serogroup 1 is responsible for 90% of patients. Within serogroup 1, large differences in prevalence in clinical isolates have been described. A recent study, using a Dutch Legionella strain collection, identified five virulence associated markers. In our study, we verify whether these five Dutch markers can predict the patient or environmental origin of a French Legionella strain collection. In addition, we identify new potential virulence markers and verify whether these can predict better. A total of 219 French patient isolates and environmental strains were compared using a mixed-genome micro-array. The micro-array data were analysed to identify predictive markers, using a Random Forest algorithm combined with a logistic regression model. The sequences of the identified markers were compared with eleven known Legionella genomes, using BlastN and BlastX; the functionality for each of the predictive markers was checked in the literature.Results: The five Dutch markers insufficiently predicted the patient or environmental origin of the French Legionella strains. Subsequent analyses identified four predictive markers for the French collection that were used for the logistic regression model. This model showed a negative predictive value of 91%. Three of the French markers differed from the Dutch markers, one showed considerable overlap and was found in one of the Legionella genomes (Lorraine strain). This marker encodes for a structural toxin protein RtxA, described for L. pneumophila as a factor involved in virulence and entry in both human cells and amoebae.Conclusions: The combination of a mixed-genome micro-array and statistical analysis using a Random Forest algorithm has identified virulence markers in a consistent way. The Lorraine strain and related Dutch and French Legionella strains contain a marker that encodes a RtxA protein which probably is involved in the increased prevalence in clinical isolates. The current set of predictive markers is insufficient to justify its use as a reliable test in the public health field in France. Our results suggest that genetic differences in Legionella strains exist between geographically distinct entities. It may be necessary to develop region-specific mixed-genome microarrays that are constantly adapted and updated. © 2013 Den Boer et al.; licensee BioMed Central Ltd.

Published
2013

31. Factors associated with hospital mortality in community-acquired legionellosis in France

Author

Chidiac, C., Che, D., Pires-Cronenberger, S., Jarraud, S., Campèse, C., Bissery, A., Weinbreck, P., Brun-Buisson, C., Sollet, J.-P., Ecochard, R., Desenclos, J.-C., Etienne, J., Vanhems, Philippe, Renseigné, Non, Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), 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)-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), 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), Département santé environnement, Institut de Veille Sanitaire (INVS), Immunité infection vaccination (I2V), and Université de Lyon-Université de Lyon-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, Multivariate analysis, [SDV]Life Sciences [q-bio], MESH: Legionnaires' Disease, Kaplan-Meier Estimate, Disease, 0302 clinical medicine, MESH: Aged, 80 and over, Adrenal Cortex Hormones, Risk Factors, MESH: Risk Factors, Hospital Mortality, Prospective Studies, 030212 general & internal medicine, Young adult, Prospective cohort study, Aged, 80 and over, MESH: Aged, 0303 health sciences, MESH: Middle Aged, Middle Aged, MESH: Predictive Value of Tests, Anti-Bacterial Agents, 3. Good health, Community-Acquired Infections, MESH: Community-Acquired Infections, MESH: Young Adult, Predictive value of tests, Radiological weapon, Female, France, Legionnaires' Disease, Adult, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Adolescent, Corticosteroid treatment, Hospital mortality, MESH: Multivariate Analysis, Legionella pneumophila, MESH: Adrenal Cortex Hormones, Young Adult, 03 medical and health sciences, Predictive Value of Tests, Internal medicine, MESH: Anti-Bacterial Agents, medicine, Humans, MESH: Hospital Mortality, MESH: Kaplan-Meier Estimate, Aged, MESH: Adolescent, MESH: Humans, 030306 microbiology, business.industry, MESH: Adult, MESH: Legionella pneumophila, MESH: Prospective Studies, MESH: Male, Surgery, MESH: France, Multivariate Analysis, business, MESH: Female
Abstract

International audience; The aims of this study were to describe the clinical, biological and radiological features of community-acquired (CA) Legionnaires' disease (LD) and identify the predictors of mortality in hospitalised patients. Demographic data, risk factors, clinical and biological features, medical management, complications, and outcome from 540 hospitalised patients with confirmed CA LD were prospectively recorded. 8.1% of patients (44 out of 540) died. The predictors of survival after Kaplan-Meier analysis were male sex (p = 0.01), age 500 mg * L(-1) (RH 2.14, 95% CI 1.02-4.48). Appropriate antibiotic therapy was prescribed for 70.8% (292 out of 412) of patients after admission and for 99.8% (537 out of 538) of patients after diagnosis confirmation. In conclusion, female sex, age, ICU stay, renal failure, corticosteroid treatment and increased level of CRP are significant risk factors for mortality in CA LD.

Published
2012

32. Insertion sequences as highly resolutive genomic markers for sequence type 1 \textitLegionella pneumophila Paris

Author

Vergnes, M., Ginevra, C., Kay, E., Normand, Philippe, Thioulouse, J., Jarraud, S., Maurin, M., Schneider, D., Laboratoire d'Ecologie Microbienne - UMR 5557 (LEM), Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Vétérinaire de Lyon (ENVL)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)

Subjects
[SDV]Life Sciences [q-bio]
Published
2011

35. Comparative analyses of Legionella species identifies genetic features of strains causing Legionnaires' disease

Author

Gomez-Valero, L, Rusniok, C, Rolando, M, Neou, M, Dervins-Ravault, D, Demirtas, J, Rouy, Z, Moore, RJ, Chen, H, Petty, NK, Jarraud, S, Etienne, J, Steinert, M, Heuner, K, Gribaldo, S, Medigue, C, Gloeckner, G, Hartland, EL, Buchrieser, C, Gomez-Valero, L, Rusniok, C, Rolando, M, Neou, M, Dervins-Ravault, D, Demirtas, J, Rouy, Z, Moore, RJ, Chen, H, Petty, NK, Jarraud, S, Etienne, J, Steinert, M, Heuner, K, Gribaldo, S, Medigue, C, Gloeckner, G, Hartland, EL, and Buchrieser, C

Abstract

BACKGROUND: The genus Legionella comprises over 60 species. However, L. pneumophila and L. longbeachae alone cause over 95% of Legionnaires’ disease. To identify the genetic bases underlying the different capacities to cause disease we sequenced and compared the genomes of L. micdadei, L. hackeliae and L. fallonii (LLAP10), which are all rarely isolated from humans. RESULTS: We show that these Legionella species possess different virulence capacities in amoeba and macrophages, correlating with their occurrence in humans. Our comparative analysis of 11 Legionella genomes belonging to five species reveals highly heterogeneous genome content with over 60% representing species-specific genes; these comprise a complete prophage in L. micdadei, the first ever identified in a Legionella genome. Mobile elements are abundant in Legionella genomes; many encode type IV secretion systems for conjugative transfer, pointing to their importance for adaptation of the genus. The Dot/Icm secretion system is conserved, although the core set of substrates is small, as only 24 out of over 300 described Dot/Icm effector genes are present in all Legionella species. We also identified new eukaryotic motifs including thaumatin, synaptobrevin or clathrin/coatomer adaptine like domains. CONCLUSIONS: Legionella genomes are highly dynamic due to a large mobilome mainly comprising type IV secretion systems, while a minority of core substrates is shared among the diverse species. Eukaryotic like proteins and motifs remain a hallmark of the genus Legionella. Key factors such as proteins involved in oxygen binding, iron storage, host membrane transport and certain Dot/Icm substrates are specific features of disease-related strains.

Published
2014

36. Host-Related Risk Factors and Clinical Features of Community-Acquired Legionnaires Disease Due to the Paris and Lorraine Endemic Strains 1998-2007

Author

Ginevra, C., Duclos, A., Vanhems, Philippe, Campèse, C., Forey, F., Lina, G., Che, D., Etienne, J., Jarraud, S., Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), and 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)

Subjects
[SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT]
Published
2009

37. ETUDE PROSPECTIVE DE 21 CAS DE PNEUMONIE NOSOSCOMIALE A LEGIONNELLA PNEUMOPHILA SURVENUS EN FRANCE, AVRIL 2006-JUIN 2007

Author

Pires-Cronenberger, S., Chidiac, C., Campèse, D., Che, D., Bissery, A., Jarraud, S., Etienne, S., Brun-Buisson, C., Weinbreck, Pierre, Poirier, R., Vanhems, Philippe, Equipe de Recherche Médicale Appliquée (ERMA), Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Service des Maladies infectieuses et tropicales [CHU Limoges], and CHU Limoges

Subjects
[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

ERMA

Published
2008

38. NEUMONIE NOSOCOMIALE A LEGIONNELLA PNEUMOPHILA : ETUDE PROSPECTIVE DE 21 CAS SURVENUS EN FRANCE (AVRIL 2006-JUIN 2007)

Author

Pires-Cronenberger, S., Chidiac, C., Weinbreck, Pierre, Campèse, D., Che, D., Bissery, A., Jarraud, S., Jérôme, C., Brun-Buisson, C., Poirier, R., Vanhems, Philippe, Service des Maladies infectieuses et tropicales [CHU Limoges], CHU Limoges, Equipe de Recherche Médicale Appliquée (ERMA), and Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Université de Limoges (UNILIM)-CHU Limoges

Subjects
[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

ERMA

Published
2008

39. LEGIONELLA ET LEGIONELLOSES EN FRANCE EN 2008

Author

Vanhems, Philippe, Pires-Cronenberger, S., Campèse, C., Che, D., Bissery, A., Ecochard, D., Jarraud, S., Etienne, C., Brun-Buisson, C., Poirier, P., Weinbreck, Pierre, Service des Maladies infectieuses et tropicales [CHU Limoges], CHU Limoges, Equipe de Recherche Médicale Appliquée (ERMA), Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Université de Limoges (UNILIM)-CHU Limoges, and Merigaud, Françoise

Subjects
[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

ERMA

Published
2008

42. Experimental and theoretical evaluation of typing methods based upon random amplification of genomic restriction fragments (AFLP) for bacterial population genetics

Author

Mougel, Christophe, Teyssier, Sabrina, D'Angelo, C., Groud, K., Neyra, M., Sidi-Boumedine, K., Cloeckaert, Axel, PELOILLE, Michèle, Baucheron, Sylvie, Chaslus-Dancla, E., Jarraud, S., Meugnier, H., Forey, F., Vandenesch, François, Lina, Gérard, Etienne, J., Thioulouse, Jean, Manceau, C., Robbe, P., Nalin, R., Briolay, J., Nesme, Xavier, Station de Pathologie aviaire et parasitologie [Nouzilly] (PAP), Institut National de la Recherche Agronomique (INRA), and Unité de recherche Pathologie végétale et phytobactériologie

Subjects
[SDV.GEN]Life Sciences [q-bio]/Genetics, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2001

43. egc, a hyfhly prevalent operon of enterotixin gene, forms a putative nursery of superantigens in Staphylococcus aureus

Author

Jarraud, S., Peyrat, M.A., Lim, A., Tristan, A., Bes, M., Mougel, Christophe, Etienne, J., Vandenesch, François, Bonneville, M., Lina, Gérard, Microbiologie, Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB), and ProdInra, Migration

Subjects
[SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2001

44. Analysis of the Legionella longbeachae Genome and Transcriptome Uncovers Unique Strategies to Cause Legionnaires' Disease

Author

Matic, I, Cazalet, C, Gomez-Valero, L, Rusniok, C, Lomma, M, Dervins-Ravault, D, Newton, HJ, Sansom, FM, Jarraud, S, Zidane, N, Ma, L, Bouchier, C, Etienne, J, Hartland, EL, Buchrieser, C, Matic, I, Cazalet, C, Gomez-Valero, L, Rusniok, C, Lomma, M, Dervins-Ravault, D, Newton, HJ, Sansom, FM, Jarraud, S, Zidane, N, Ma, L, Bouchier, C, Etienne, J, Hartland, EL, and Buchrieser, C

Abstract

Legionella pneumophila and L. longbeachae are two species of a large genus of bacteria that are ubiquitous in nature. L. pneumophila is mainly found in natural and artificial water circuits while L. longbeachae is mainly present in soil. Under the appropriate conditions both species are human pathogens, capable of causing a severe form of pneumonia termed Legionnaires' disease. Here we report the sequencing and analysis of four L. longbeachae genomes, one complete genome sequence of L. longbeachae strain NSW150 serogroup (Sg) 1, and three draft genome sequences another belonging to Sg1 and two to Sg2. The genome organization and gene content of the four L. longbeachae genomes are highly conserved, indicating strong pressure for niche adaptation. Analysis and comparison of L. longbeachae strain NSW150 with L. pneumophila revealed common but also unexpected features specific to this pathogen. The interaction with host cells shows distinct features from L. pneumophila, as L. longbeachae possesses a unique repertoire of putative Dot/Icm type IV secretion system substrates, eukaryotic-like and eukaryotic domain proteins, and encodes additional secretion systems. However, analysis of the ability of a dotA mutant of L. longbeachae NSW150 to replicate in the Acanthamoeba castellanii and in a mouse lung infection model showed that the Dot/Icm type IV secretion system is also essential for the virulence of L. longbeachae. In contrast to L. pneumophila, L. longbeachae does not encode flagella, thereby providing a possible explanation for differences in mouse susceptibility to infection between the two pathogens. Furthermore, transcriptome analysis revealed that L. longbeachae has a less pronounced biphasic life cycle as compared to L. pneumophila, and genome analysis and electron microscopy suggested that L. longbeachae is encapsulated. These species-specific differences may account for the different environmental niches and disease epidemiology of these two Legionella species

Published
2010

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