Absence of Specific Chlamydia trachomatis Inclusion Membrane Proteins Triggers Premature Inclusion Membrane Lysis and Host Cell Death

Publication date: 16 May 2017
Source:Cell Reports, Volume 19, Issue 7
Author(s): Mary M. Weber, Jennifer L. Lam, Cheryl A. Dooley, Nicholas F. Noriea, Bryan T. Hansen, Forrest H. Hoyt, Aaron B. Carmody, Gail L. Sturdevant, Ted Hackstadt
Chlamydia trachomatis is a human pathogen associated with significant morbidity worldwide. As obligate intracellular parasites, chlamydiae must survive within eukaryotic cells for sufficient time to complete their developmental cycle. To promote host cell survival, chlamydiae express poorly understood anti-apoptotic factors. Using recently developed genetic tools, we show that three inclusion membrane proteins (Incs) out of eleven examined are required for inclusion membrane stability and avoidance of host cell death pathways. In the absence of specific Incs, premature inclusion lysis results in recognition by autophagolysosomes, activation of intrinsic apoptosis, and premature termination of the chlamydial developmental cycle. Inhibition of autophagy or knockdown of STING prevented host cell death and activation of intrinsic apoptosis. Significantly, these findings emphasize the importance of Incs in the establishment of a replicative compartment that sequesters the pathogen from host surveillance systems.

Graphical abstract

Teaser

Weber el al use genetic means to disrupt Chlamydia trachomatis proteins essential for parasitophorous vacuole (inclusion) membrane stability. Premature inclusion lysis exposes chlamydiae to the cytosol to induce autophagic and apoptotic pathways. Understanding how normally anti-apoptotic chlamydiae induce apoptosis will help define mechanisms of chlamydial intracellular survival.


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