The Role of ESX-1 in Mycobacterium tuberculosis Pathogenesis

Microbiology Spectrum
Ka-Wing Wong

Abstract

In this article, we have described several cellular pathological effects caused by the Mycobacterium tuberculosis ESX-1. The effects include induction of necrosis, NOD2 signaling, type I interferon production, and autophagy. We then attempted to suggest that these pathological effects are mediated by the cytosolic access of M. tuberculosis-derived materials as a result of the phagosome-disrupting activity of the major ESX-1 substrate ESAT-6. Such activity of ESAT-6 is most likely due to its pore-forming activity at the membrane. The amyloidogenic characteristic of ESAT-6 is reviewed here as a potential mechanism of membrane pore formation. In addition to ESAT-6, the ESX-1 substrate EspB interferes with membrane-mediated innate immune mechanisms such as efferocytosis and autophagy, most likely through its ability to bind phospholipids. Overall, the M. tuberculosis ESX-1 secretion system appears to be a specialized system for the deployment of host membrane-targeting proteins, whose primary function is to interrupt key steps in innate immune mechanisms against pathogens. Inhibitors that block the ESX-1 system or block host factors critical for ESX-1 toxicity have been identified and should represent attractive potential new antit...Continue Reading

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May 16, 2018·Pathogens and Disease·S UpadhyayJ A Philips
Aug 2, 2018·Médecine sciences : M/S·Jeanne GuittonMarie-Pierre Golinelli-Cohen
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Nov 23, 2021·Frontiers in Microbiology·Yingyu ChenAizhen Guo

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