ESX-1 and phthiocerol dimycocerosates of Mycobacterium tuberculosis act in concert to cause phagosomal rupture and host cell apoptosis - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Cellular Microbiology Année : 2017

ESX-1 and phthiocerol dimycocerosates of Mycobacterium tuberculosis act in concert to cause phagosomal rupture and host cell apoptosis

Roxane Simeone
Fadel Sayes
Roland Brosch

Résumé

Although phthiocerol dimycocerosates (DIM) are major virulence factors of Mycobacterium tuberculosis (Mtb), the causative agent of human tuberculosis, little is known about their mechanism of action. Localized in the outer membrane of mycobacterial pathogens, DIM are predicted to interact with host cell membranes. Interaction with eukaryotic membranes is a property shared with another virulence factor of Mtb, the early secretory antigenic target EsxA (also known as ESAT‐6). This small protein, which is secreted by the type VII secretion system ESX‐1 (T7SS/ESX‐1), is involved in phagosomal rupture and cell death induced by virulent mycobacteria inside host phagocytes. In this work, by the use of several knock‐out or knock‐in mutants of Mtb or Mycobacterium bovis BCG strains and different cell biological assays, we present conclusive evidence that ESX‐1 and DIM act in concert to induce phagosomal membrane damage and rupture in infected macrophages, ultimately leading to host cell apoptosis. These results identify an as yet unknown function for DIM in the infection process and open up a new research field for the study of the interaction of lipid and protein virulence factors of Mtb.

Dates et versions

hal-02326055 , version 1 (22-10-2019)

Identifiants

Citer

Jacques Augenstreich, Ainhoa Arbues, Roxane Simeone, Evert Haanappel, Alice Wegener, et al.. ESX-1 and phthiocerol dimycocerosates of Mycobacterium tuberculosis act in concert to cause phagosomal rupture and host cell apoptosis. Cellular Microbiology, 2017, 19 (7), pp.e12726. ⟨10.1111/cmi.12726⟩. ⟨hal-02326055⟩
68 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More