title: The distinct fate of smooth and rough Mycobacterium abscessus variants inside macrophages.
abstract: Mycobacterium abscessus is a pathogenic, rapidly growing mycobacterium responsible for pulmonary and cutaneous infections in immunocompetent patients and in patients with Mendelian disorders, such as cystic fibrosis (CF). Mycobacterium abscessus is known to transition from a smooth (S) morphotype with cell surface-associated glycopeptidolipids (GPL) to a rough (R) morphotype lacking GPL. Herein, we show that M. abscessus S and R variants are able to grow inside macrophages and are present in morphologically distinct phagosomes. The S forms are found mostly as single bacteria within phagosomes characterized by a tightly apposed phagosomal membrane and the presence of an electron translucent zone (ETZ) surrounding the bacilli. By contrast, infection with the R form leads to phagosomes often containing more than two bacilli, surrounded by a loose phagosomal membrane and lacking the ETZ. In contrast to the R variant, the S variant is capable of restricting intraphagosomal acidification and induces less apoptosis and autophagy. Importantly, the membrane of phagosomes enclosing the S forms showed signs of alteration, such as breaks or partial degradation. Although not frequently encountered, these events suggest that the S form is capable of provoking phagosome-cytosol communication. In conclusion, M. abscessus S exhibits traits inside macrophages that are reminiscent of slow-growing mycobacterial species.
authors.affiliation: UMR1173, Inserm and UFR Des Sciences de la Santé Simone Veil, Université de Versailles Saint Quentin, Montigny, France.
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Roux
authors.affiliation: Centre National de la Recherche Scientifique FRE 3689, Centre d'études d'agents Pathogènes et Biotechnologies pour la Santé, Université de Montpellier, 1919, Route de Mende, 34293, Montpellier, France.|Centre d'Immunologie de Marseille-Luminy, Aix-Marseille Université UM 2, Inserm, U1104, CNRS UMR7280, 13288, Marseille, France.
authors.forename: Albertus
authors.initials: A
authors.lastname: Viljoen
authors.affiliation: CNRS, Institut de Pharmacologie et de Biologie Structurale (IPBS), UMR 5089 CNRS/Université Paul Sabatier, 205 route de Narbonne, BP 64182, 31077 Toulouse Cedex 4, France.
authors.forename: Aïcha
authors.initials: A
authors.lastname: Bah
authors.affiliation: Unité de Pathogénomique mycobactérienne, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, Paris, France.
authors.forename: Roxane
authors.initials: R
authors.lastname: Simeone
authors.affiliation: Centre National de la Recherche Scientifique FRE 3689, Centre d'études d'agents Pathogènes et Biotechnologies pour la Santé, Université de Montpellier, 1919, Route de Mende, 34293, Montpellier, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Bernut
authors.affiliation: UMR1173, Inserm and UFR Des Sciences de la Santé Simone Veil, Université de Versailles Saint Quentin, Montigny, France.
authors.forename: Laura
authors.initials: L
authors.lastname: Laencina
authors.affiliation: UMR1179, Inserm and UFR Des Sciences de la Santé Simone Veil, Université de Versailles Saint Quentin, Montigny, France.
authors.forename: Therese
authors.initials: T
authors.lastname: Deramaudt
authors.affiliation: UMR1173, Inserm and UFR Des Sciences de la Santé Simone Veil, Université de Versailles Saint Quentin, Montigny, France.
authors.forename: Martin
authors.initials: M
authors.lastname: Rottman
authors.affiliation: UMR1173, Inserm and UFR Des Sciences de la Santé Simone Veil, Université de Versailles Saint Quentin, Montigny, France.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Gaillard
authors.affiliation: Unité de Pathogénomique mycobactérienne, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, Paris, France.
authors.forename: Laleh
authors.initials: L
authors.lastname: Majlessi
authors.affiliation: Unité de Pathogénomique mycobactérienne, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, Paris, France.
authors.forename: Roland
authors.initials: R
authors.lastname: Brosch
authors.affiliation: UMR1173, Inserm and UFR Des Sciences de la Santé Simone Veil, Université de Versailles Saint Quentin, Montigny, France.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Girard-Misguich
authors.affiliation: CNRS, Institut de Pharmacologie et de Biologie Structurale (IPBS), UMR 5089 CNRS/Université Paul Sabatier, 205 route de Narbonne, BP 64182, 31077 Toulouse Cedex 4, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Vergne
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix-Marseille Université UM 2, Inserm, U1104, CNRS UMR7280, 13288, Marseille, France.
authors.forename: Chantal
authors.initials: C
authors.lastname: de Chastellier
authors.affiliation: Centre National de la Recherche Scientifique FRE 3689, Centre d'études d'agents Pathogènes et Biotechnologies pour la Santé, Université de Montpellier, 1919, Route de Mende, 34293, Montpellier, France laurent.kremer@cpbs.cnrs.fr.|INSERM, CPBS, 34293 Montpellier, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Kremer
authors.affiliation: UMR1173, Inserm and UFR Des Sciences de la Santé Simone Veil, Université de Versailles Saint Quentin, Montigny, France jean-louis.herrmann@aphp.fr.
authors.forename: Jean-Louis
authors.identifier: 0000-0003-2347-6418
authors.initials: JL
authors.lastname: Herrmann
mesh_terms: D002478:Cells, Cultured; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D008264:Macrophages / Q000382:microbiology*; D009165:Mycobacterium Infections, Nontuberculous / Q000382:microbiology; D016926:Mycobacterium chelonae / Q000254:growth & development*; D010588:Phagosomes / Q000382:microbiology
keywords: Mycobacterium abscessus; innate response; macrophages; phagosome; rapid-growing mycobacteria