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1. Tracking Animal Reservoirs of Pathogenic Leptospira: The Right Test for the Right Claim

Author

Koussay Dellagi, Patrick Mavingui, Pablo Tortosa, Yann Gomard, Steve Michael Goodman, Processus Infectieux en Milieu Insulaire Tropical (PIMIT), Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IRD-Centre National de la Recherche Scientifique (CNRS), Direction Internationale de l'Institut Pasteur, Institut Pasteur [Paris] (IP), Association Vahatra [Antananarivo, Madagascar], Field Museum of Natural History [Chicago, USA], The sampling of Mormopterus acetabulosus on Mauritius was supported by a grant from European Research Development Fund (ERDF) 'Pathogènes associés à la Faune Sauvage Océan Indien' #31189. Original serological data presented in this paper were obtained under a grant from ERDF known as InterregV ECOSPIR 'Eco-épidemiologie des leptospires endémiques de l’Océan Indien: des bactéries à risque pour les populations humaines?' (number RE6875)., Tortosa, Pablo, Centre National de la Recherche Scientifique (CNRS)-IRD-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de La Réunion (UR), and Institut Pasteur [Paris]

Subjects
Leptospira, 030231 tropical medicine, Zoology, Context (language use), Biology, Article, Microbiology, Serology, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Direct agglutination test, medicine, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, One Health, 030304 developmental biology, 0303 health sciences, animal reservoir, MAT, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, General Immunology and Microbiology, 030306 microbiology, Zoonosis, Public Health, Environmental and Occupational Health, [SDV.BA.MVSA] Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, Gold standard (test), medicine.disease, biology.organism_classification, Leptospirosis, 3. Good health, Chronic infection, Infectious Diseases, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Medicine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.MP.PAR] Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology
Abstract

Leptospirosis, caused by a pathogenic Leptospira bacteria, is the most prevalent zoonosis worldwide and in this context has been extensively investigated through a One Health framework. Diagnosis of human leptospirosis includes molecular and serological tools, with serological Microscopic Agglutination Test (MAT) still being considered as a gold standard. Mammals considered as biological reservoirs include species or populations that are able to maintain chronic infection and shed the bacteria via their urine in the environment. Leptospira bacteria are often investigated using the same diagnosis tool, serological MAT. However, MAT testing of putative animal reservoirs can lead to mis-interpretations as it can signal previous infection and not necessarily bring in robust information regarding the capacity of such sero-positive animals to maintain chronic infection. We use previously published data and present new results on introduced and endemic small mammals to show that MAT should not be used for the identification of reservoirs. By contrast, serological data are informative on the level of exposure of animals occupying a specific environment. Finally, we present a sequential methodology to investigate human leptospirosis in a One Health framework that associates molecular detection in humans and animals, together with MAT of human samples using Leptospira isolates obtained from reservoir animals occurring in the same environment.

Published
2021

2. Potential of Aedes albopictus and Aedes aegypti (Diptera: Culicidae) to transmit yellow fever virus in urban areas in Central Africa

Author

Basile Kamgang, Aurelie P. Yougang, Theodel A. Wilson-Bahun, Armel N. Tedjou, Charles S. Wondji, Laurence Mousson, Anna-Bella Failloux, Marie Vazeille, Centre for Research in Infectious Diseases [Yaoundé] (CRID), Arbovirus et Insectes Vecteurs - Arboviruses and Insect Vectors, Institut Pasteur [Paris] (IP), Université de Yaoundé I, University Marien Ngouabi of Brazzaville (umng), Liverpool School of Tropical Medicine (LSTM), This study was supported by a Wellcome Trust Training Fellowship in Public Health and Tropical Medicine [grant number 204862/Z/16/Z] awarded to BK., We would like to thank the populations of different collection sites for their collaboration during the field works. BK, CSW and ABF designed the experiments. BK performed the research. MV and LM provided a technical help. ANT, APY, TAWB helped in mosquito collections, BK, CSW and ABF wrote the paper with contribution from all other authors., and Institut Pasteur [Paris]

Subjects
0301 basic medicine, medicine.medical_specialty, Aedes albopictus, Epidemiology, 030106 microbiology, Immunology, wa_395, Mosquito Vectors, Aedes aegypti, Microbiology, Article, law.invention, 03 medical and health sciences, Aedes, law, Virology, Yellow Fever, Drug Discovery, parasitic diseases, medicine, Animals, Humans, qx_525, Africa, Central, Socioeconomics, yellow fever virus, vector competence, Central Africa, biology, Public health, Yellow fever, Outbreak, General Medicine, biology.organism_classification, medicine.disease, wc_530, 3. Good health, 030104 developmental biology, Infectious Diseases, Geography, Transmission (mechanics), Vector (epidemiology), [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Female, Parasitology
Abstract

International audience; Yellow Fever (YF) remains a major public health issue in Sub-Saharan Africa and South America, despite the availability of an effective vaccine. In Africa, most YF outbreaks are reported in West Africa. However, urban outbreaks occurred in 2016 in both Angola and the Democratic Republic of Congo (DRC), and imported cases were reported in Chinese workers coming back from Africa. In Central Africa, Cameroon and the Republic of Congo host a high proportion of non-vaccinated populations increasing the risk of urban outbreaks. The main vector is Aedes aegypti and possibly, Aedes albopictus, both being anthropophilic and domestic mosquitoes. Here, we provide evidence that both Ae. aegypti and Ae. albopictus in Cameroon and the Republic of Congo are able to transmit Yellow fever virus (YFV) with higher rates of infection, dissemination, and transmission for Ae. aegypti. We conclude that the potential of both Aedes species to transmit YFV could increase the risk of urban YF transmission and urge public health authorities to intensify their efforts to control domestic vectors, and extend vaccine coverage to prevent major YFV outbreak.

Published
2019

3. Optimization of a magnetic bead-based assay (MAGPIX®-Luminex) for immune surveillance of exposure to malaria using multiple Plasmodium antigens and sera from different endemic settings

Author

Aissata Basse, Inès Vigan-Womas, Alioune Dieye, Cheikh Loucoubar, Babacar Mbengue, Marie Louise Varela, Ronald Perraut, Aissatou Touré, Institut Pasteur de Dakar, Réseau International des Instituts Pasteur (RIIP), Institut Pasteur de Madagascar, Département Parasites et Insectes vecteurs - Department of Parasites and Insect Vectors, Institut Pasteur [Paris], This study was supported by grants from Institut Pasteur Fondation, from Rotary International, ACIP (Institut Pasteur, N°25_2012) and EDCTP—European & Developing Countries Clinical Trials Partnership., We thank Dr Odile Mercereau-Puijalon and Dr Shirley Longacre for constant support and providing antigens, we are grateful to Dr Shirley Longacre for revising this paper. We thank Drs Marc Jouan and Jérôme Salomon from Division International (Institut Pasteur, Paris) for their help to initiate this work in the very early steps. We are grateful to the villagers of Dielmo and Ndiop for their active participation and continuing collaboration in the project and Pr Bacary Diatta for help providing hospital samples., and Institut Pasteur [Paris] (IP)

Subjects
0301 basic medicine, lcsh:Arctic medicine. Tropical medicine, lcsh:RC955-962, 030231 tropical medicine, Plasmodium falciparum, Protozoan Proteins, Antigens, Protozoan, Plasmodium malariae, Biology, lcsh:Infectious and parasitic diseases, Serology, 03 medical and health sciences, 0302 clinical medicine, Antigen, parasitic diseases, medicine, lcsh:RC109-216, Multiplex, Malaria, Falciparum, IgG response, Immunoassay, medicine.diagnostic_test, Immunomagnetic Separation, Magnetic beads assay, Methodology, medicine.disease, biology.organism_classification, 3. Good health, Malaria, 030104 developmental biology, Infectious Diseases, Immunology, biology.protein, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Parasitology, Antibody, Biomarkers
Abstract

International audience; Background: Serological markers are potentially useful tools for monitoring the progress of malaria control programs , but a better understanding of antibody response dynamics is necessary. The use of a magnetic bead-based immunoassay (MBA) is advantageous compared to ELISA, due to its multiplexing capacity, but limited information is available on the standardization and validation of this assay. Methods: Several parameters for multiplex testing of antibodies to Plasmodium antigens were analysed using a set of 4 antigens and 98 sera from Senegalese rural asymptomatic and urban symptomatic individuals. The 4 antigens included Plasmodium falciparum CSP and PfAMA1 peptides, recombinant P. falciparum MSP4p20 and a Plasmodium malariae CSP (PmCSP) peptide. Comparisons with ELISA were done using MSP4p20 and whole schizont extract (SE) antigens.Results: The use of fewer beads (1000 beads per well instead of 2000) and 5 µg of antigen per 10 6 bead were validated as lower amounts. The use of a carrier protein (BSA) was shown to be critical when using peptides and the effect of a 24 h delayed measures was evaluated (5-25% signal decrease). Analysis of Ab responses showed almost equally high levels and prevalence in all transmission settings. Clear distinctions between rural and urban malaria were noted using PmCSP and SE antigens.Conclusions: This study underlines the importance of further optimization of the MBA technique and highlights the interest of using multistage/multispecies antigens for surveillance of malaria in endemic settings.

Published
2018

4. Characterization of antibody response in neuroinvasive infection caused by Toscana virus

Author

Giada Rossini, Rémi N. Charrel, Vittorio Sambri, Silvia Morini, P. Cenni, Caterina Vocale, Nazli Ayhan, M. P. Landini, Anna Pierro, Paolo Gaibani, Stefania Varani, Michele Bartoletti, Antonio Mastroianni, F. Prati, Luigi Raumer, S. Schivazappa, Russell E. Lewis, S. Ficarelli, CRREM Laboratory [Bologna, Italy] (Unit of Microbiology), University hospital - Policlinico S.Orsola-Malpighi [Bologna, Italy], Unit of Microbiology [Pievesestina, Italy] (The Romagna Hub Laboratory), The Romagna Hub Laboratory [Pievesestina, Italy], Emergence des Pathologies Virales (EPV), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Medical and Surgical Science [Bologna, Italy] (Infectious Disease Unit), University of Bologna/Università di Bologna, Infectious Disease Unit [Forlì, Italy], G.B. Morgagni-Pierantoni Hospital [Forlì, Italy], Infectious Disease Division [Reggio Emilia, Italy], Reggio Emilia Hospital [Italy], Emergency Department [Imola, Italy], Imola Hospital S. Maria della Scaletta [Imola, Italy], Department of Experimental, Diagnostic and Specialty Medicine [Bologna, Italy] (DIMES), Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), This work was supported by the University of Bologna (RFO2013e2015 to SV, MPL) and by the Emilia-Romagna Region (Lab P3 funds). This work was also supported in part by the European Virus Archive goes Global (EVAg) project that has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 653316 (to RNC), the EDENext FP7- n261504 EU project (to RNC) and this paper is catalogued by the EDENext Steering Committee (http://www.edenext.eu) as EDENext467. The work of RNC was done under the frame of EurNegVec COST Action TD1303., European Project: 653316,H2020,H2020-INFRAIA-2014-2015,EVAg(2015), European Project: 261504,EC:FP7:HEALTH,FP7-HEALTH-2010-single-stage,EDENEXT(2011), University of Bologna, BUISINE, Soline, European Virus Archive goes global - EVAg - - H20202015-04-01 - 2019-03-31 - 653316 - VALID, Biology and control of vector-borne infections in Europe - EDENEXT - - EC:FP7:HEALTH2011-01-01 - 2015-06-30 - 261504 - VALID, Pierro, A., Ficarelli, S., Ayhan, N., Morini, S., Raumer, L., Bartoletti, M., Mastroianni, A., Prati, F., Schivazappa, S., Cenni, P., Vocale, C., Rossini, G., Gaibani, P., Sambri, V., Landini, M.P., Lewis, R.E., Charrel, R.N., and Varani, S.

Subjects
Adult, Male, 0301 basic medicine, Microbiology (medical), Patients' follow-up, IgG avidity test, 030231 tropical medicine, 030106 microbiology, Antibodies, Viral, Bunyaviridae Infections, Antibody production, Neutralizing antibodies, Immunoglobulin G, Neutralization, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Neutralizing antibodie, medicine, Humans, Avidity, Toscana virus infection, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, biology, Toscana virus, Meningoencephalitis, Sandfly fever Naples virus, General Medicine, Middle Aged, medicine.disease, biology.organism_classification, Antibodies, Neutralizing, Meningitis, Viral, Virology, 3. Good health, Infectious Diseases, Immunoglobulin M, Immunology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, biology.protein, Female, Antibody, Meningitis
Abstract

Among sandfly-borne pathogens, Toscana virus (TOSV) is a prominent cause of summer meningitis in Mediterranean Europe. Here, we assessed the kinetics of anti-TOSV antibodies over time in 41 patients diagnosed with TOSV-meningitis or meningoencephalitis in North-eastern Italy. Objectives: Among sandfly-borne pathogens, Toscana virus (TOSV) is a prominent cause of summer meningitis in Mediterranean Europe. Here, we assessed the kinetics of anti-TOSV antibodies over time in 41 patients diagnosed with TOSV meningitis or meningoencephalitis in northeastern Italy. Methods: Acute and follow-up serum samples were collected up to 20 months after diagnosis of TOSV infection and tested for the presence of specific antibody using immunoenzymatic and indirect immunofluorescence assays. In addition, maturation of anti-TOSV IgG over time was evaluated as well as production of neutralizing antibodies. Results: Specific IgM and IgG response was present at diagnosis in 100% of patients; TOSV-specific IgM and IgG were detected in patients' sera up to 6 and 20 months after diagnosis, respectively. The avidity index (AI) increased over the first month after infection in 100% of patients and most cases exceeded 60% by Day 30 post infection. The AI subsequently plateaued then declined at 20 months after diagnosis. Finally, neutralization assay to TOSV was performed in 217 sera collected from 41 patients; 69.6% of tested samples resulted in reactive and moderate levels of neutralizing antibodies observed during all phases of infection despite high titres of total anti-TOSV IgG. Conclusions: Specific antibody response develops rapidly and is long-lasting for neuroinvasive TOSV infection. Serodiagnosis of neuroinvasive TOSV requires simultaneous detection of specific IgM and IgG. Moderate levels of neutralizing antibodies were maintained over the study period, while the protective role of antibodies lacking neutralizing activity is unclear and requires further evaluation.

Published
2017

5. Purinergic Signaling: A Common Path in the Macrophage Response against Mycobacterium tuberculosis and Toxoplasma gondii

Author

Laetitia Petit-Jentreau, Ludovic Tailleux, Janine L. Coombes, University of Liverpool, Pathogénomique mycobactérienne intégrée, Institut Pasteur [Paris] (IP), Génétique mycobactérienne - Mycobacterial genetics, The present work was supported by the University of Liverpool. JLC is a lecturer at the University of Liverpool, UK, LT is a researcher at Institut Pasteur, France, and LP-J is a postdoctoral researcher on the JLC's Biotechnology and Biological Sciences Research Council (BBSRC) grant (BB/M023540/1) at the University of Liverpool, UK., LP-J wrote the paper with input from LT and JLC. All authors revised the manuscript, and approved it for publication., and Institut Pasteur [Paris]

Subjects
0301 basic medicine, Microbiology (medical), Immunology, lcsh:QR1-502, Toxoplasma gondii, Microbiology, lcsh:Microbiology, 03 medical and health sciences, Immune system, Purinergic Agents, Macrophage, innate immunity, Innate immune system, biology, Intracellular parasite, Purinergic receptor, Mycobacterium tuberculosis, biology.organism_classification, purinergic agents, nucleotides, 3. Good health, macrophages, ATP, 030104 developmental biology, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Intracellular
Abstract

International audience; Immune responses are essential for the protection of the host against external dangers or infections and are normally efficient in the clearance of invading microbes. However, some intracellular pathogens have developed strategies to replicate and survive within host cells resulting in latent infection associated with strong inflammation. This excessive response can cause cell and tissue damage and lead to the release of the intracellular content, in particular the nucleotide pool, into the extracellular space. Over the last decade, new studies have implicated metabolites from the purinergic pathway in shaping the host immune response against intracellular pathogens and proved their importance in the outcome of the infection. This review aims to summarize how the immune system employs the purinergic system either to fight the pathogen, or to control collateral tissue damage. This will be achieved by focusing on the macrophage response against two intracellular pathogens, the human etiologic agent of tuberculosis, Mycobacterium tuberculosis and the protozoan parasite, Toxoplasma gondii.

Published
2017
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6. High Rates of Neutralizing Antibodies to Toscana and Sandfly Fever Sicilian Viruses in Livestock, Kosovo

Author

Kurtesh Sherifi, Rémi N. Charrel, Kristaq Berxholi, Arber Taraku, Nazli Ayhan, Emergence des Pathologies Virales (EPV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM), University of Prishtina, Agricultural University of Tirana, This work was supported in part by the European Virus Archive Goes Global project, which has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement no. 653316, the EDENext FP7-no. 261504 European Union project and this paper is catalogued by the EDENext Steering Committee as EDENext469 (http://www.edenext.eu). The work of N.A. and R.N.C. was conducted under the frame of EurNegVec COST Action TD1303. N.A. is supported by the Fondation Mediterranee Infection., European Project: 653316,H2020,H2020-INFRAIA-2014-2015,EVAg(2015), European Project: 261504,EC:FP7:HEALTH,FP7-HEALTH-2010-single-stage,EDENEXT(2011), BUISINE, Soline, European Virus Archive goes global - EVAg - - H20202015-04-01 - 2019-03-31 - 653316 - VALID, and Biology and control of vector-borne infections in Europe - EDENEXT - - EC:FP7:HEALTH2011-01-01 - 2015-06-30 - 261504 - VALID

Subjects
0301 basic medicine, Phlebovirus, Epidemiology, Kosovo, vector-borne infections, lcsh:Medicine, Mediterranean, Antibodies, Viral, 0302 clinical medicine, Phlebotomus Fever, Sandfly Fever Sicilian Virus, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Toscana virus, biology, Incidence, Dispatch, 3. Good health, Infectious Diseases, Epidemiological Monitoring, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Bunyaviridae, Microbiology (medical), Livestock, 030231 tropical medicine, Arbovirus, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, Balkan, medicine, Animals, Humans, lcsh:RC109-216, viruses, sandfly fever Sicilian virus, Sheep, lcsh:R, Sandfly fever Naples virus, biology.organism_classification, medicine.disease, Antibodies, Neutralizing, Virology, Insect Vectors, Sandfly, 030104 developmental biology, arbovirus, High Rates of Neutralizing Antibodies to Toscana and Sandfly Fever Sicilian Viruses in Livestock, Kosovo, Cattle, Psychodidae, sand flies
Abstract

Kurtesh Sherifi and Rémi N. Charrel contributed equally to this article; International audience; Toscana and sandfly fever Sicilian viruses (TOSV and SFSV, respectively), both transmitted by sand flies, are prominent human pathogens in the Old World. Of 1,086 serum samples collected from cattle and sheep during 2013 in various regions of Kosovo (Balkan Peninsula), 4.7% and 53.4% had neutralizing antibodies against TOSV and SFSV, respectively.

Published
2017

7. Helicobacter pylori Adapts to Chronic Infection and Gastric Disease via pH-Responsive BabA-Mediated Adherence

Author

Verena Königer, D. Scott Merrell, Roman Andriiovych Moskalenko, Rainer Haas, Thomas Borén, Sara Henriksson, Jafar Mahdavi, Abhijit Chowdhury, Johan Ögren, Anders Hofer, Jay V. Solnick, Dan Danielsson, Sara K. Lindén, Dag Ilver, Konstantinos S. Papadakos, Susanne Vikström, Jörgen Ådén, Jan Holgersson, Gerhard Gröbner, Alexej Schmidt, Jeanna Bugaytsova, Oscar Björnham, Göran O. Bylund, Rolf Sjöström, Stefan Oscarson, Dionyssios N. Sgouras, Lori M. Hansen, Yevgen A Chernov, Anders Esberg, Kristof Moonens, Christopher Aisenbrey, Charles Kelly, Ludmilla A. Morozova-Roche, Jeannette M. Whitmire, Beatriz Martinez-Gonzalez, Asish K. Mukhopadhyay, Angela Eldridge, Nicklas Strömberg, Robert H. Gilman, Andre Dubois, Lars Engstrand, Staffan Schedin, Brett A. Chromy, Justine Younson, Matthew Goldman, Anna Shevtsova, Macarena P. Quintana-Hayashi, Hui Liu, Magnus Unemo, Lena Rakhimova, Anna Åberg, Sebastian Suerbaum, Anna Arnqvist, Pär Gideonsson, Maréne Landström, Douglas E. Berg, Kristoffer Brännström, Anders Olofsson, Melissa Mendez, G. Balakrish Nair, Han Remaut, Umeå University, School of Life Sciences, University of Nottingham, UK (UON), Sahlgrenska Academy at University of Gothenburg [Göteborg], Université libre de Bruxelles (ULB), VIB-VUB Center for Structural Biology [Bruxelles], VIB [Belgium], Sumy State University, Max Von Pettenkofer Institute (MVP), Ludwig-Maximilians-Universität München (LMU), Uniformed Services University of the Health Sciences (USUHS), King‘s College London, Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU), School of Digestive and Liver Diseases [Kolkata] (SDLD), National Institute of Cholera and Enteric Diseases, Translational Health Science and Technology Institute [Faridabad] (THSTI), Institut Pasteur Hellénique, Réseau International des Instituts Pasteur (RIIP), Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Karolinska Institutet [Stockholm], Örebro University Hospital [Örebro, Sweden], Hannover Medical School [Hannover] (MHH), German Center for Infection Research - partner site Hannover-Braunschweig (DZIF), School of Chemistry and Chemical Biology (UCD), University College Dublin [Dublin] (UCD), University of California [Davis] (UC Davis), University of California, German Center for Infection Research, Partnersite Munich (DZIF), Département d'Informatique [Bruxelles] (ULB), Faculté des Sciences [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), University of California [San Diego] (UC San Diego), This work was supported by grants from Vetenskapsrådet (VR/M) to T.B. and S.K.L., Cancerfonden to T.B. and A.A., VR/NT to A.A. and S. Schedin, Formas to S.K.L., the J.C. Kempe and Seth M. Kempe Memorial Foundation, the Knut and Alice Wallenberg Foundation (2012.0090) to T.B. and M.L., European Union Seventh Framework Program GastricGlycoExplorer ITN grant number 316929 to T.B. and Y.A.C., Magn. Bergvall’s Foundation to S. Schedin, DFG (SFB 900/A1) to S. Suerbaum, DFG (HA2697/16-1) to R.H., FP6 ANR-06-PATHO-00701 ERA-NET and Actions Concertées Inter-Pasteuriennes (ACIP) (2006) to D.N.S., NIH R01DK063041 to D.E.B., NIH CA082312 to D.S.M., NIH AI070803 and AI081037 to J.V.S., CSIR project, India (No. 37(1640)/14/EMR –II) to A.K.M., and VIB and FWO (grants: G033717N and 12H8416N) to K.M. and H.R., This paper is dedicated to the memory of our friend, collaborator, and co-author Dr. Andre Dubois, a great scientist who contributed importantly both intellectually and materially to this project. We thank S. Michopoulos and G. Mantzaris for H. pylori clinical isolates and Ö. Furberg (NoPolo.se), N. Ulander (softplanbangkok.com), S. Lindström, and M. Borén for the digital movie, tech, art, and figure work, respectively., Vrije Universiteit Brussel, Basic (bio-) Medical Sciences, Structural Biology Brussels, and Department of Bio-engineering Sciences

Subjects
0301 basic medicine, MESH: Hydrogen-Ion Concentration, Gastric acidity, MESH: Helicobacter Infections/pathology, MESH: Helicobacter pylori/physiology, Disease, adaptation, Bacterial Adhesion, polymorphism, acid responsiveness, MESH: Bacterial Adhesion, Bacterial, Hydrogen-Ion Concentration, gastric acidity, Adhesins, 3. Good health, Cell and molecular biology, medicine.anatomical_structure, Infectious Diseases, MESH: Gastric Mucosa/microbiology, Medical Microbiology, 030106 microbiology, Immunology, Digestive Diseases - (Peptic Ulcer), Biology, blood group antigen-binding adhesion, Microbiology, Helicobacter Infections, diversity, Vaccine Related, 03 medical and health sciences, Virology, ABO blood group system, Biodefense, Gastric mucosa, medicine, MESH: Helicobacter Infections/microbiology, multimerization, Adhesins, Bacterial, subpopulations, Helicobacter pylori, Prevention, gastric cancer, MESH: Adhesins, Bacterial/metabolism, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Gastric Mucosa/pathology, Bacterial adhesin, Chronic infection, 030104 developmental biology, Emerging Infectious Diseases, Gastric Mucosa, Parasitology, Digestive Diseases
Abstract

The BabA adhesin mediates high-affinity binding of Helicobacter pylori to the ABO blood group antigen-glycosylated gastric mucosa. Here we show that BabA is acid responsive-binding is reduced at low pH and restored by acid neutralization. Acid responsiveness differs among strains; often correlates with different intragastric regions and evolves during chronic infection and disease progression; and depends on pH sensor sequences in BabA and on pH reversible formation of high-affinity binding BabA multimers. We propose that BabA's extraordinary reversible acid responsiveness enables tight mucosal bacterial adherence while also allowing an effective escape from epithelial cells and mucus that are shed into the acidic bactericidal lumen andthat bio-selection and changes in BabA bindingproperties through mutation and recombination with babA-related genes are selected by differencesamong individuals and by changes in gastric acidity over time. These processes generate diverse H.pylori subpopulations, in which BabA's adaptive evolution contributes to H.pylori persistence and overt gastric disease.

Published
2017

8. Description of compensatory gyrA mutations restoring fluoroquinolone susceptibility in Mycobacterium tuberculosis

Author

Stéphanie Petrella, Alexandra Aubry, Nicolas Veziris, Hélène Ferrand, Claudine Mayer, Aurélie Bouige, Alix Pantel, Stéphanie Matrat, Wladimir Sougakoff, Université Pierre et Marie Curie - Paris 6 (UPMC), Microbiologie structurale - Structural Microbiology (Microb. Struc. (UMR_3528 / U-Pasteur_5)), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Parts of this paper were presented at the ‘International Conference on Antimicrobial Agents and Chemotherapy’, USA, 2011 (C1-626), and at the EMBO Conference ‘Tuberculosis 2012’, France, 2012 (TUBERCULOSIS2012/000269)., Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence des Mycobactéries et de la Résistance aux Antituberculeux [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre National de Référence des Mycobactéries et de la Résistance des Mycobactéries aux Antituberculeux, Bactériologie-Hygiène [CHU Pitié-Salpêtrière] ], and CHU Pitié-Salpêtrière [APHP]

Subjects
0301 basic medicine, MESH: Mycobacterium tuberculosis, DNA Mutational Analysis, Mutant, Antitubercular Agents, medicine.disease_cause, DNA gyrase, MESH: Recombinant Proteins, Suppression, Genetic, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Pharmacology (medical), MESH: DNA Mutational Analysis, MESH: Suppression, Genetic, MESH: Inhibitory Concentration 50, Mutation, MESH: Microbial Sensitivity Tests, biology, Chemistry, MESH: Escherichia coli, Recombinant Proteins, 3. Good health, MESH: Mutagenesis, Site-Directed, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, DNA Gyrase, DNA supercoil, Fluoroquinolones, medicine.drug, MESH: DNA Gyrase, Microbiology (medical), 030106 microbiology, Mutation, Missense, Microbial Sensitivity Tests, Microbiology, Mycobacterium tuberculosis, Inhibitory Concentration 50, 03 medical and health sciences, Drug Resistance, Bacterial, MESH: Drug Resistance, Bacterial, Escherichia coli, medicine, Humans, Pharmacology, MESH: Mutation, Missense, MESH: Humans, Mutagenesis, MESH: Fluoroquinolones, biology.organism_classification, MESH: Antitubercular Agents, Mutagenesis, Site-Directed, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Ofloxacin
Abstract

International audience; OBJECTIVES:Resistance to fluoroquinolones (FQs) in Mycobacterium tuberculosis (Mtb) is mainly due to mutations in DNA gyrase (GyrA2B2), with the most common substitutions located at positions 90 and 94 in GyrA. Two clinical MDR Mtb (MDR-TB) strains harbouring an A90E or D94N substitution in GyrA were found to be surprisingly susceptible to FQs (ofloxacin MIC ≤2 mg/L). We studied the impact of the additional GyrA substitutions found in these strains (T80A and T80A + A90G, respectively) on FQ susceptibility.METHODS:Mutants of interest were generated by site-specific mutagenesis of GyrA alleles. WT and mutant TB DNA gyrase subunits were overexpressed in Escherichia coli and purified, and the in vitro susceptibility to FQs of their DNA supercoiling reaction was studied.RESULTS:IC50s of mutant gyrase complexes bearing GyrA D94N and A90E were 3- to 36-fold higher than WT IC50s, whereas IC50s of gyrase bearing T80A + A90G + D94N and T80A + A90E were close to the WT IC50s.CONCLUSIONS:We demonstrated that substitutions T80A and A90G restore FQ susceptibility when associated with a substitution implicated in high-level FQ resistance. Line probe assay misclassification of MDR-TB strains as pre-XDR or XDR can be corrected by sequence analysis of gyrA.

Published
2016

9. Integrated Analysis of Environment, Cattle and Human Serological Data: Risks and Mechanisms of Transmission of Rift Valley Fever in Madagascar

Author

Annelise Tran, Vladimir Grosbois, Jean-Pierre Ravalohery, Fanjasoa Rakotomanana, Jean-Michel Heraud, Soa Fy Andriamandimby, Christophe Rogier, Seta Andriamamonjy, Véronique Chevalier, Benoit Durand, Marie-Marie Olive, Animal et gestion intégrée des risques (UPR AGIRs), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Unité de Virologie [Antananarivo, Madagascar] (IPM), Institut Pasteur de Madagascar, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Laboratoire de santé animale, sites de Maisons-Alfort et de Dozulé, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Réseau International des Instituts Pasteur (RIIP), This study was supported in part by funds raised by (i) CIRAD (ii) the Centre National d'Etudes Spatiales (CNES, grant # 131163/00) (iii) the Institut Pasteur de Madagascar. Human field work was funded by the Institut Pasteur of Madagascar (Internal Project through the ZORA (ZOonoses, Rodent and Arboviruses) project and the Centers for Disease Control and Prevention (CDC, and Cooperative Agreement #U51/IP000327). Moreover, this material is based upon work supported by the U. S. Department of Homeland Security under the Center of Excellence of Emerging and Zoonotic Animal Diseases Grant Award Number 2010-ST061-AG0001. Cattle study was supported in part by funds raised by World Health Organization (WHO) and the Food and Agriculture Organization of the United Nations (FAO) through the Central Emergency Response Fund of the United Nations. The views and conclusions contained in this paper are those of the authors and should not be interpreted as necessarily representing the official policies, either explicit or implicit, of the U. S. Department of Homeland Security. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Subjects
Veterinary medicine, Epidemiology, Pathology and Laboratory Medicine, law.invention, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Analyse du risque, MESH: Cattle Diseases, MESH: Animals, Neglected tropical diseases, Mammals, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, MESH: Middle Aged, 000 - Autres thèmes, Fièvre de la Vallée du Rift, Anopheles, Ruminants, 3. Good health, Transmission (mechanics), MESH: Young Adult, Densité de population, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Enzootic, Infectious diseases, L72 - Organismes nuisibles des animaux, Genre humain, Bétail, Livestock, lcsh:RC955-962, MESH: Culex, Microbiology, MESH: Anopheles, 03 medical and health sciences, MESH: Cross-Sectional Studies, Madagascar, MESH: Humans, MESH: Seroepidemiologic Studies, Tropical diseases, Public Health, Environmental and Occupational Health, Organisms, lcsh:RA1-1270, MESH: Adult, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, 15. Life on land, medicine.disease, Invertebrates, Insect Vectors, 030104 developmental biology, Africa, Cattle, MESH: Female, MESH: Antibodies, Viral, 0301 basic medicine, RNA viruses, Cattle Diseases, Disease Vectors, L73 - Maladies des animaux, Mosquitoes, Serology, Geographical Locations, MESH: Madagascar, law, Zoonoses, Facteur de risque, Bunyaviruses, Medicine and Health Sciences, MESH: Rift Valley Fever, Comportement humain, Rift Valley fever, 2. Zero hunger, biology, lcsh:Public aspects of medicine, Agriculture, Facteur du milieu, Medical microbiology, Insects, MESH: Cattle, Vecteur de maladie, Vertebrates, Viruses, MESH: Rift Valley fever virus, Seasons, Pathogens, Research Article, lcsh:Arctic medicine. Tropical medicine, Zone humide, Arthropoda, Distribution géographique, Culex, 030231 tropical medicine, Viral diseases, MESH: Insect Vectors, Virus de la fièvre de la vallée du Rift, Sérologie, Bovines, medicine, Seroprevalence, Animals, MESH: Environment, Transmission des maladies, Biology and life sciences, Viral pathogens, Morbidité, biology.organism_classification, Rift Valley fever virus, MESH: Male, Microbial pathogens, Amniotes, People and Places, Earth Sciences, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
Abstract

Background Rift Valley fever (RVF) is a vector-borne disease affecting ruminants and humans. Madagascar was heavily affected by RVF in 2008–2009, with evidence of a large and heterogeneous spread of the disease. The identification of at-risk environments is essential to optimize the available resources by targeting RVF surveillance in Madagascar. Herein, the objectives of our study were: (i) to identify the environmental factors and areas favorable to RVF transmission to both cattle and human and (ii) to identify human behaviors favoring human infections in Malagasy contexts. Methodology/Principal Findings First, we characterized the environments of Malagasy communes using a Multiple Factor Analysis (MFA). Then, we analyzed cattle and human serological data collected at national level using Generalized Linear Mixed Models, with the individual serological status (cattle or human) as the response, and MFA factors, as well as other potential risk factors (cattle density, human behavior) as explanatory variables. Cattle and human seroprevalence rates were positively associated to humid environments (p, Author Summary Rift Valley fever virus (RVFV) is a pathogen that causes a vector-borne tropical disease. The disease affects ruminants and humans and severely impacts the health and economy of affected countries. Madagascar was heavily affected by Rift Valley fever (RVF) in 2008–2009, with evidence of a large and heterogeneous spread of the disease. Our study aims at identifying environmental and human-related risk factors for RVFV transmission. First, we characterized Malagasy environments according to their putative influence on RVFV mosquito density and population dynamics. Then we statistically analyzed cattle and human serological data collected at a national level with the individual serological status as response, and Malagasy environments previously characterized by climatic and landscape variables as well as other potential risk factors as explanatory variables. Our results identified humid environments of the western, north-western and eastern parts of the island as risky areas. The identification of at-risk environments is essential to focus veterinary surveillance and control of RVFV.

Published
2016

10. Neutrophil Extracellular Traps are Involved in the Innate Immune Response to Infection with Leptospira

Author

Emilia Scharrig, María Florencia Ferrer, Agostina Carestia, Mathieu Picardeau, Maia Cédola, Ricardo Martín Gómez, Mirta Schattner, Gabriela Pretre, Ricardo Drut, CCT La Plata-CONICET-Facultad de Ciencias Veterinarias [La Plata, PBA, Argentine], Universidad Nacional de la Plata [Argentine] (UNLP), Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET), Children Hospital 'Superiora Sor María Ludovica' LA PLATA, Biologie des Spirochètes / Biology of Spirochetes, Institut Pasteur [Paris], This work was supported by PICTs grant 12-0434 (RMG) and 11-733 (MS) from ANPCyT. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript., Conceived and designed the experiments: MP MS RMG. Performed the experiments: ES AC MFF GP. Analyzed the data: MC RD. Contributed reagents/materials/analysis tools: MP. Wrote the paper: MS RMG., and Institut Pasteur [Paris] (IP)

Subjects
Male, lcsh:Arctic medicine. Tropical medicine, Neutrophils, lcsh:RC955-962, [SDV]Life Sciences [q-bio], Inflammation, Extracellular Traps, Microbiology, purl.org/becyt/ford/1 [https], Ciencias Biológicas, Mice, 03 medical and health sciences, neutrophils, Immunity, In vivo, Leptospira, medicine, Animals, Humans, leptospirosis, Leptospirosis, purl.org/becyt/ford/1.6 [https], Ciencias Exactas, 030304 developmental biology, 0303 health sciences, Innate immune system, biology, 030306 microbiology, lcsh:Public aspects of medicine, Public Health, Environmental and Occupational Health, lcsh:RA1-1270, Nets, Neutrophil extracellular traps, biology.organism_classification, Immunity, Innate, 3. Good health, Mice, Inbred C57BL, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, medicine.symptom, Leptospira interrogans, Virología, Ex vivo, CIENCIAS NATURALES Y EXACTAS, Research Article
Abstract

NETosis is a process by which neutrophils extrude their DNA together with bactericidal proteins that trap and/or kill pathogens. In the present study, we evaluated the ability of Leptospira spp. to induce NETosis using human ex vivo and murine in vivo models. Microscopy and fluorometric studies showed that incubation of human neutrophils with Leptospira interrogans serovar Copenhageni strain Fiocruz L1-130 (LIC) resulted in the release of DNA extracellular traps (NETs). The bacteria number, pathogenicity and viability were relevant factors for induction of NETs, but bacteria motility was not. Entrapment of LIC in the NETs resulted in LIC death; however, pathogenic but not saprophytic Leptospira sp. exerted nuclease activity and degraded DNA. Mice infected with LIC showed circulating NETs after 2 days post-infection (dpi). Depletion of neutrophils with mAb1A8 significantly reduced the amount of intravascular NETs in LIC-infected mice, increasing bacteremia at 3 dpi. Although there was a low bacterial burden, scarce neutrophils and an absence of inflammation in the early stages of infection in the kidney and liver, at the beginning of the leptospiruric phase, the bacterial burden was significantly higher in kidneys of neutrophil-depleted-mice compared to non-depleted and infected mice. Surprisingly, interstitial nephritis was of similar intensity in both groups of infected mice. Taken together, these data suggest that LIC triggers NETs, and that the intravascular formation of these DNA traps appears to be critical not only to prevent early leptospiral dissemination but also to preclude further bacterial burden., Instituto de Biotecnologia y Biologia Molecular, Facultad de Ciencias Exactas, Facultad de Ciencias Médicas

Published
2015

11. Malaria risk in Corsica, former hot spot of malaria in France

Author

Gilbert Le Goff, Céline Toty, Hélène Barré, Daniel Couret, Nil Rahola, Didier Fontenille, Isabelle Larget-Thiery, Caractérisation et contrôle des populations de vecteurs, Institut de Recherche pour le Développement (IRD), Direction de la Solidarité et de la Santé de Corse et de Corse-du-Sud, Sciences pour l'environnement (SPE), Centre National de la Recherche Scientifique (CNRS)-Université Pascal Paoli (UPP), Centre de Production et Infection des Anophèles (plateforme) - Center for the Production and Infection of Anopheles (platform) (CEPIA), Institut Pasteur [Paris], The paper is catalogued by the EDEN Steering Committee as EDEN 232 http://www.eden-fp6project.net/., Université Pascal Paoli (UPP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), and Centre de Production et Infection des Anophèles (Plateforme) (CEPIA)

Subjects
Risk, Entomology, lcsh:Arctic medicine. Tropical medicine, lcsh:RC955-962, 030231 tropical medicine, Plasmodium vivax, Plasmodium falciparum, MESH: Malaria, Zoology, MESH: Insect Vectors, Biology, Plasmodium, Polymerase Chain Reaction, lcsh:Infectious and parasitic diseases, MESH: Anopheles, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Anopheles, parasitic diseases, medicine, Animals, Humans, MESH: Animals, lcsh:RC109-216, MESH: Plasmodium falciparum, 0303 health sciences, MESH: Humans, MESH: Risk, 030306 microbiology, Ecology, Research, Outbreak, MESH: Polymerase Chain Reaction, medicine.disease, biology.organism_classification, 3. Good health, Insect Vectors, Malaria, MESH: Plasmodium vivax, MESH: France, Infectious Diseases, Parasitology, France
Abstract

Background The prevalence of Plasmodium falciparum and Plasmodium vivax malaria was very high in Corsica just before the Second World War. The last outbreak was in 1972 and the most recent indigenous case was in 2006. Results Analysis of historical data shows that anopheline vectors were abundant. Recent surveys demonstrated that potential vectors are still present in Corsica, despite the likely disappearance of Anopheles sacharovi. Moreover, P. falciparum can develop experimentally into these mosquitoes, notably Anopheles labranchiae, which is locally abundant, and parasites are regularly introduced into the island. Discussion, Conclusions The presence of vectors, the introduction of parasites and the conducive climate raise questions about the possibility of malaria re-emerging and becoming re-established in Corsica. Analysis of historic and current parasitological and entomological data shows that the current theoretical risk of indigenous cases or malaria foci is negligible, particularly since there is very little contact between humans and Anopheles mosquitoes, Plasmodium carriers are reliably treated and there is a widespread vector control on the island.

Published
2010