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

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

doi:10.1016/j.celrep.2017.04.058

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

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

Mary M Weber, Jennifer L Lam, Cheryl A Dooley, Nicholas F Noriea, Bryan T Hansen, Forrest H Hoyt, Aaron B Carmody, Gail L Sturdevant and Ted Hackstadt

Cell reports (Cambridge), Vol.19(7), pp.1406-1417

05/16/2017

DOI: 10.1016/j.celrep.2017.04.058

PMCID: PMC5499683

PMID: 28514660

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Abstract

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. [Display omitted] •Inclusion membrane proteins are required for replication and in vivo infection•Incs stabilize the inclusion and sequester the bacteria from host recognition•STING targets C. trachomatis to the selective autophagy pathway•Inhibition of autophagy prevents host cell death triggered by Inc mutants 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.

apoptosis

STING

Chlamydia trachomatis

parasitophorous vacuole

autophagy

inclusion membrane proteins

Details

Title: Subtitle: Absence of Specific Chlamydia trachomatis Inclusion Membrane Proteins Triggers Premature Inclusion Membrane Lysis and Host Cell Death
Creators: Mary M Weber - Host Parasite Interactions Section, Laboratory of Bacteriology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA
Jennifer L Lam - Host Parasite Interactions Section, Laboratory of Bacteriology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA
Cheryl A Dooley - Host Parasite Interactions Section, Laboratory of Bacteriology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA
Nicholas F Noriea - Host Parasite Interactions Section, Laboratory of Bacteriology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA
Bryan T Hansen - Research Technologies Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA
Forrest H Hoyt - Research Technologies Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA
Aaron B Carmody - Research Technologies Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA
Gail L Sturdevant - Innate Immunity and Pathogenesis Section, Laboratory of Virology, Rocky Mountain Laboratories, National Institutes of Allergy and Infectious Disease, National Institutes of Health, Hamilton, MT 59840, USA
Ted Hackstadt - Host Parasite Interactions Section, Laboratory of Bacteriology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA
Resource Type: Journal article
Publication Details: Cell reports (Cambridge), Vol.19(7), pp.1406-1417
Publisher: Elsevier Inc
DOI: 10.1016/j.celrep.2017.04.058
PMID: 28514660
PMCID: PMC5499683
ISSN: 2211-1247
eISSN: 2211-1247
Grant note: DOI: 10.13039/100000060, name: National Institute of Allergy and Infectious Diseases; DOI: 10.13039/100000002, name: National Institutes of Health, award: Z01 AI000567
Language: English
Date published: 05/16/2017
Academic Unit: Molecular Physiology and Biophysics; Microbiology and Immunology
Record Identifier: 9984083266902771

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