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Microbiol Spectr. 2019 May;7(3). doi: 10.1128/microbiolspec.BAI-0024-2019.

Infect and Inject: How Mycobacterium tuberculosis Exploits Its Major Virulence-Associated Type VII Secretion System, ESX-1.

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Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461.
Department of Microbial Sciences, School of Biosciences and Medicine, University of Surrey, Guilford, Surrey, GU27XH, United Kingdom.
Department of Molecular Biology & Biochemistry and Department of Pharmaceutical Sciences, University of California Irvine, Irvine, CA 92697.


Mycobacterium tuberculosis is an ancient master of the art of causing human disease. One important weapon within its fully loaded arsenal is the type VII secretion system. M. tuberculosis has five of them: ESAT-6 secretion systems (ESX) 1 to 5. ESX-1 has long been recognized as a major cause of attenuation of the FDA-licensed vaccine Mycobacterium bovis BCG, but its importance in disease progression and transmission has recently been elucidated in more detail. This review summarizes the recent advances in (i) the understanding of the ESX-1 structure and components, (ii) our knowledge of ESX-1's role in hijacking macrophage function to set a path for infection and dissemination, and (iii) the development of interventions that utilize ESX-1 for diagnosis, drug interventions, host-directed therapies, and vaccines.

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