1. Mycobacterium abscessus Phospholipase C Expression Is Induced during Coculture within Amoebae and Enhances M. abscessus Virulence in Mice
- Author
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Jean-Louis Herrmann, Isabelle Poncin, Vincent Le Moigne, Carole Serveau-Avesque, Laura Laencina, Nathalie Soismier, Stéphane Canaan, Roland Brosch, Martin Rottman, Gilles Etienne, Fabienne Girard-Misguich, Jean-Louis Gaillard, Anne-Laure Roux, Fabien Le Chevalier, Jean Claude Bakala N'Goma, Enzymologie interfaciale et de physiologie de la lipolyse (EIPL), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Hôpital Raymond Poincaré [AP-HP], Pathogénomique mycobactérienne intégrée - Integrated Mycobacterial Pathogenomics, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Cellule Pasteur, Université Paris Diderot - Paris 7 (UPD7)-PRES Sorbonne Paris Cité, Institut de pharmacologie et de biologie structurale (IPBS), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), We thank Vaincre La Mucoviscidose (VLM IC1014 and RF20120600689) and the Région Ile-de-France (Domaine d'Intérêt Majeur Maladies Infectieuses et Emergentes) for funding the postdoctoral fellowship to V.L.M. and a Ph.D. program for F.L.C. We are also grateful for the support from the Centre National de la Recherche Scientifique (CNRS)., Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Infection et inflammation (2I), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), Vaincre la mucoviscidose (VLM): VLMIC1014 and RF20120600689, Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Epidémiologie et Physiopathologie des Infections Microbiennes (EPIM), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Cité (UPCité)-Microbiologie Intégrative et Moléculaire (UMR6047), and Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
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Cystic Fibrosis ,Virulence Factors ,[SDV]Life Sciences [q-bio] ,Immunology ,Mycobacterium Infections, Nontuberculous ,Mycobacterium chelonae ,Virulence ,Mycobacterium abscessus ,medicine.disease_cause ,Microbiology ,Mycobacterium ,Gene Knockout Techniques ,Membrane Lipids ,Mice ,medicine ,Animals ,Amoeba ,Cells, Cultured ,Mice, Inbred BALB C ,Base Sequence ,biology ,Phospholipase C ,Macrophages ,Mycobacterium smegmatis ,Pathogenic bacteria ,Sequence Analysis, DNA ,bacterial infections and mycoses ,biology.organism_classification ,Molecular Pathogenesis ,[SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology ,Coculture Techniques ,Recombinant Proteins ,Infectious Diseases ,Type C Phospholipases ,bacteria ,Protozoa ,Parasitology ,Genome, Bacterial - Abstract
Mycobacterium abscessus is a pathogenic, rapidly growing mycobacterium involved in pulmonary and cutaneo-mucous infections worldwide, to which cystic fibrosis patients are exquisitely susceptible. The analysis of the genome sequence of M. abscessus showed that this bacterium is endowed with the metabolic pathways typically found in environmental microorganisms that come into contact with soil, plants, and aquatic environments, where free-living amoebae are frequently present. M. abscessus also contains several genes that are characteristically found only in pathogenic bacteria. One of them is MAB_0555 , encoding a putative phospholipase C (PLC) that is absent from most other rapidly growing mycobacteria, including Mycobacterium chelonae and Mycobacterium smegmatis . Here, we report that purified recombinant M. abscessus PLC is highly cytotoxic to mouse macrophages, presumably due to hydrolysis of membrane phospholipids. We further showed by constructing and using an M. abscessus PLC knockout mutant that loss of PLC activity is deleterious to M. abscessus intracellular survival in amoebae. The importance of PLC is further supported by the fact that M. abscessus PLC was found to be expressed only in amoebae. Aerosol challenge of mice with M. abscessus strains that were precultured in amoebae enhanced M. abscessus lung infectivity relative to M. abscessus grown in broth culture. Our study underlines the importance of PLC for the virulence of M. abscessus . Despite the difficulties of isolating M. abscessus from environmental sources, our findings suggest that M. abscessus has evolved in close contact with environmental protozoa, which supports the argument that amoebae may contribute to the virulence of opportunistic mycobacteria.
- Published
- 2015
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