AUTHOR=Danelishvili Lia , Everman Jamie , McNamara Michael , Bermudez Luiz 

TITLE=Inhibition of the Plasma-Membrane-Associated Serine Protease Cathepsin G by Mycobacterium tuberculosis Rv3364c Suppresses Caspase-1 and Pyroptosis in Macrophages

JOURNAL=Frontiers in Microbiology

VOLUME=2

YEAR=2012

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2011.00281

DOI=10.3389/fmicb.2011.00281

ISSN=1664-302X

ABSTRACT=<p>Tuberculosis is a disease associated with the infection of a great part of the world’s population and is responsible for the death of two to three million people annually. <italic>Mycobacterium tuberculosis</italic> infects macrophages and subverts its mechanisms of killing. The pathogen suppresses macrophage apoptosis by many different mechanisms. We describe that, upon uptake by macrophages, <italic>M. tuberculosis</italic> overexpresses an operon Rv3361c-Rv3365c and secretes Rv3364c. The Rv3365c knockout strain is deficient in apoptosis inhibition. The Rv3364c protein binds to the serine protease cathepsin G on the membrane, inhibiting its enzymatic activity and the downstream activation of caspase-1-dependent apoptosis. In summary, <italic>M. tuberculosis</italic> prevents macrophage pyroptosis by a novel mechanism involving cytoplasmic surveillance proteins.</p>