Revisiting the role of phospholipases C in virulence and the lifecycle of Mycobacterium tuberculosis

Fabien Le Chevalier (1, 2) , Alessandro Cascioferro (1) , Wafa Frigui (1) , Alexandre Pawlik (1) , Eva C. Boritsch (1) , Daria Bottai (3) , Laleh Majlessi (1) , Jean Louis Herrmann (4, 5, 6) , Roland Brosch (1)

1 Pathogénomique mycobactérienne intégrée
2 Cellule Pasteur
3 Dipartimento di Ricerca Traslazionale e delle Nuove Tecnologie in Medicina e Chirurgia
4 2I - Infection et inflammation
5 UVSQ Santé - Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil
6 Service de Microbiologie [Garches]

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.

Mots clés: Infection; Pathogens

Domaines: Biochimie [q-bio.BM]; Génomique, Transcriptomique et Protéomique [q-bio.GN]; Maladies infectieuses

Fabien Le Chevalier, Alessandro Cascioferro, Wafa Frigui, Alexandre Pawlik, Eva C. Boritsch, et al.. Revisiting the role of phospholipases C in virulence and the lifecycle of Mycobacterium tuberculosis. Scientific Reports, 2015, 5 (1), pp.16918. ⟨10.1038/srep16918⟩. ⟨pasteur-02618632⟩