title: Revisiting the role of phospholipases C in virulence and the lifecycle of Mycobacterium tuberculosis.
abstract: 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.
authors.affiliation: Institut Pasteur, Unit for Integrated Mycobacterial Pathogenomics, F-75015, Paris, France.|Université Paris Diderot, Sorbonne Paris Cité, Cellule Pasteur, Paris, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Le Chevalier
authors.affiliation: Institut Pasteur, Unit for Integrated Mycobacterial Pathogenomics, F-75015, Paris, France.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cascioferro
authors.affiliation: Institut Pasteur, Unit for Integrated Mycobacterial Pathogenomics, F-75015, Paris, France.
authors.forename: Wafa
authors.initials: W
authors.lastname: Frigui
authors.affiliation: Institut Pasteur, Unit for Integrated Mycobacterial Pathogenomics, F-75015, Paris, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Pawlik
authors.affiliation: Institut Pasteur, Unit for Integrated Mycobacterial Pathogenomics, F-75015, Paris, France.
authors.forename: Eva C
authors.initials: EC
authors.lastname: Boritsch
authors.affiliation: Dipartimento di Ricerca Traslazionale e delle Nuove Tecnologie in Medicina e Chirurgia, University of Pisa, Italy.
authors.forename: Daria
authors.initials: D
authors.lastname: Bottai
authors.affiliation: Institut Pasteur, Unit for Integrated Mycobacterial Pathogenomics, F-75015, Paris, France.
authors.forename: Laleh
authors.initials: L
authors.lastname: Majlessi
authors.affiliation: INSERM U1173, UFR Sciences de la Santé Simone Veil, Université Versailles-Saint-Quentin, 78180 Saint-Quentin en Yvelines, France.|Service de Microbiologie, Hôpital Raymond Poincaré, Assistance Publique Hôpitaux de Paris, 92380 Garches, France.
authors.forename: Jean Louis
authors.initials: JL
authors.lastname: Herrmann
authors.affiliation: Institut Pasteur, Unit for Integrated Mycobacterial Pathogenomics, F-75015, Paris, France.
authors.forename: Roland
authors.initials: R
authors.lastname: Brosch
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D003124:Colorimetry; D005260:Female; D006801:Humans; D008018:Life Cycle Stages; D008168:Lung / Q000382:microbiology; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D009169:Mycobacterium tuberculosis / Q000201:enzymology* / Q000472:pathogenicity*; D009876:Operon / Q000235:genetics; D010588:Phagosomes / Q000378:metabolism; D010713:Phosphatidylcholines / Q000378:metabolism; D013154:Spleen / Q000382:microbiology; D014376:Tuberculosis / Q000201:enzymology* / Q000382:microbiology / Q000473:pathology; D010738:Type C Phospholipases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014774:Virulence / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D010713:Phosphatidylcholines; D010738:Type C Phospholipases