Revisiting the role of phospholipases C in virulence and the lifecycle of Mycobacterium tuberculosis
| Autor: | Wafa Frigui, Fabien Le Chevalier, Alexandre Pawlik, Roland Brosch, Jean-Louis Herrmann, Daria Bottai, Laleh Majlessi, Alessandro Cascioferro, Eva C. Boritsch |
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| Přispěvatelé: | Pathogénomique mycobactérienne intégrée, Institut Pasteur [Paris], Cellule Pasteur, Université Paris Diderot - Paris 7 (UPD7)-PRES Sorbonne Paris Cité, Dipartimento di Ricerca Traslazionale e delle Nuove Tecnologie in Medicina e Chirurgia, University of Pisa - Università di Pisa, Infection et inflammation (2I), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Service de Microbiologie [Garches], Hôpital Raymond Poincaré [AP-HP], We acknowledge the support by the Agence National de Recherche (ANR-14-JAMR-001-02) and the Fondation pour la Recherche Médicale FRM (DEQ20130326471). R.B. is a member of the LabEx consortium IBEID at the Institut Pasteur. E.C.B. was supported by a stipend from the Pasteur–Paris University (PPU) International PhD program and the Institut Carnot Pasteur Maladies Infectieuses. F.L-C was supported by the French Region Ile-de- France (Domaine d’Intérêt Majeur Maladies Infectieuses et Emergentes) PhD program., We are grateful to Graham F. Hatfull for providing the mycobacterial recombineering vector pJV53. Mycobacterial knock-out strain Myc2509ΔPLC and the M. tuberculosis MT103 parental strain used as controls, were a gift from Brigitte Gicquel, strain M. tuberculosis H37RvΔRD1 was a gift from William R. Jacobs, Jr. We thank Karim Sébastien for expert assistance in animal care in biosafety-A3 facilities., Institut Pasteur [Paris] (IP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM) |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
MESH: Mycobacterium tuberculosis
Operon MESH: Spleen Mutant Mice SCID MESH: Virulence Mice [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases Phagosomes MESH: Colorimetry MESH: Animals MESH: Tuberculosis MESH: Mice SCID Lung MESH: Bacterial Proteins Phagosome 0303 health sciences Multidisciplinary Virulence biology 3. Good health Phosphatidylcholines Colorimetry Female Pathogens MESH: Type C Phospholipases Infection MESH: Operon Tuberculosis Article Cell Line Microbiology Mycobacterium tuberculosis 03 medical and health sciences MESH: Phagosomes Bacterial Proteins MESH: Mice Inbred C57BL [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry Molecular Biology/Genomics [q-bio.GN] medicine Animals Humans MESH: Lung [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry Molecular Biology/Biochemistry [q-bio.BM] Gene MESH: Life Cycle Stages MESH: Mice 030304 developmental biology Life Cycle Stages MESH: Humans 030306 microbiology Macrophages MESH: Macrophages Type C Phospholipases MESH: Phosphatidylcholines biology.organism_classification medicine.disease MESH: Cell Line Mice Inbred C57BL MESH: Female Spleen Bacteria |
| Zdroj: | Scientific Reports Scientific Reports, Nature Publishing Group, 2015, 5 (1), pp.16918. ⟨10.1038/srep16918⟩ Scientific Reports, 2015, 5 (1), pp.16918. ⟨10.1038/srep16918⟩ |
| ISSN: | 2045-2322 |
| Popis: | Mycobacterium tuberculosis, the agent of human tuberculosis has developed different virulence mechanisms and virulence-associated tools during its evolution to survive and multiply inside the host. Based on previous reports and by analogy with other bacteria, phospholipases C (PLC) of M. tuberculosis were thought to be among these tools. To get deeper insights into the function of PLCs, we investigated their putative involvement in the intracellular lifestyle of M. tuberculosis, with emphasis on phagosomal rupture and virulence, thereby re-visiting a research theme of longstanding interest. Through the construction and use of an M. tuberculosis H37Rv PLC-null mutant (ΔPLC) and control strains, we found that PLCs of M. tuberculosis were not required for induction of phagosomal rupture and only showed marginal, if any, impact on virulence of M. tuberculosis in the cellular and mouse infection models used in this study. In contrast, we found that PLC-encoding genes were strongly upregulated under phosphate starvation and that PLC-proficient M. tuberculosis strains survived better than ΔPLC mutants under conditions where phosphatidylcholine served as sole phosphate source, opening new perspectives for studies on the role of PLCs in the lifecycle of M. tuberculosis. |
| Databáze: | OpenAIRE |
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