Open AccessThe C terminus of the mycobacterium ESX-1 secretion system substrate ESAT-6 is required for phagosomal membrane damage and virulence
Author(s) -
Morwan M. Osman,
Jonathan K. Shanahan,
Frances Chu,
Kevin K. Takaki,
Malte L. Pinckert,
Antonio J. Pagán,
Roland Brosch,
William H. Conrad,
Lalita Ramakrishnan
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2122161119
Subject(s) - virulence , phagosome , mycobacterium marinum , microbiology and biotechnology , secretion , mycobacterium tuberculosis , biology , esat 6 , macrophage , mycobacterium , tuberculosis , phagocytosis , virology , bacteria , gene , biochemistry , medicine , in vitro , genetics , pathology
Significance Tuberculosis (TB), an ancient disease of humanity, continues to be a major cause of worldwide death. The causative agent of TB,Mycobacterium tuberculosis , and its close pathogenic relativeMycobacterium marinum , initially infect, evade, and exploit macrophages, a major host defense against invading pathogens. Within macrophages, mycobacteria reside within host membrane–bound compartments called phagosomes. Mycobacterium-induced damage of the phagosomal membranes is integral to pathogenesis, and this activity has been attributed to the specialized mycobacterial secretion system ESX-1, and particularly to ESAT-6, its major secreted protein. Here, we show that the integrity of the unstructured ESAT-6 C terminus is required for macrophage phagosomal damage, granuloma formation, and virulence.