Absence of Specific Chlamydia trachomatis Inclusion Membrane Proteins Triggers Premature Inclusion Membrane Lysis and Host Cell Death
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 understo...
Main Authors: | , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Elsevier
2017-05-01
|
Series: | Cell Reports |
Subjects: | |
Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124717305697 |
id |
doaj-f5a3e4432a4a498695a12044bfce22e6 |
---|---|
record_format |
Article |
spelling |
doaj-f5a3e4432a4a498695a12044bfce22e62020-11-24T21:21:03ZengElsevierCell Reports2211-12472017-05-011971406141710.1016/j.celrep.2017.04.058Absence of Specific Chlamydia trachomatis Inclusion Membrane Proteins Triggers Premature Inclusion Membrane Lysis and Host Cell DeathMary M. Weber0Jennifer L. Lam1Cheryl A. Dooley2Nicholas F. Noriea3Bryan T. Hansen4Forrest H. Hoyt5Aaron B. Carmody6Gail L. Sturdevant7Ted Hackstadt8Host Parasite Interactions Section, Laboratory of Bacteriology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USAHost Parasite Interactions Section, Laboratory of Bacteriology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USAHost Parasite Interactions Section, Laboratory of Bacteriology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USAHost Parasite Interactions Section, Laboratory of Bacteriology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USAResearch Technologies Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USAResearch Technologies Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USAResearch Technologies Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USAInnate Immunity and Pathogenesis Section, Laboratory of Virology, Rocky Mountain Laboratories, National Institutes of Allergy and Infectious Disease, National Institutes of Health, Hamilton, MT 59840, USAHost Parasite Interactions Section, Laboratory of Bacteriology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USAChlamydia 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.http://www.sciencedirect.com/science/article/pii/S2211124717305697Chlamydia trachomatisinclusion membrane proteinsparasitophorous vacuoleapoptosisautophagySTING |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
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 |
spellingShingle |
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 Absence of Specific Chlamydia trachomatis Inclusion Membrane Proteins Triggers Premature Inclusion Membrane Lysis and Host Cell Death Cell Reports Chlamydia trachomatis inclusion membrane proteins parasitophorous vacuole apoptosis autophagy STING |
author_facet |
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 |
author_sort |
Mary M. Weber |
title |
Absence of Specific Chlamydia trachomatis Inclusion Membrane Proteins Triggers Premature Inclusion Membrane Lysis and Host Cell Death |
title_short |
Absence of Specific Chlamydia trachomatis Inclusion Membrane Proteins Triggers Premature Inclusion Membrane Lysis and Host Cell Death |
title_full |
Absence of Specific Chlamydia trachomatis Inclusion Membrane Proteins Triggers Premature Inclusion Membrane Lysis and Host Cell Death |
title_fullStr |
Absence of Specific Chlamydia trachomatis Inclusion Membrane Proteins Triggers Premature Inclusion Membrane Lysis and Host Cell Death |
title_full_unstemmed |
Absence of Specific Chlamydia trachomatis Inclusion Membrane Proteins Triggers Premature Inclusion Membrane Lysis and Host Cell Death |
title_sort |
absence of specific chlamydia trachomatis inclusion membrane proteins triggers premature inclusion membrane lysis and host cell death |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2017-05-01 |
description |
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. |
topic |
Chlamydia trachomatis inclusion membrane proteins parasitophorous vacuole apoptosis autophagy STING |
url |
http://www.sciencedirect.com/science/article/pii/S2211124717305697 |
work_keys_str_mv |
AT marymweber absenceofspecificchlamydiatrachomatisinclusionmembraneproteinstriggersprematureinclusionmembranelysisandhostcelldeath AT jenniferllam absenceofspecificchlamydiatrachomatisinclusionmembraneproteinstriggersprematureinclusionmembranelysisandhostcelldeath AT cheryladooley absenceofspecificchlamydiatrachomatisinclusionmembraneproteinstriggersprematureinclusionmembranelysisandhostcelldeath AT nicholasfnoriea absenceofspecificchlamydiatrachomatisinclusionmembraneproteinstriggersprematureinclusionmembranelysisandhostcelldeath AT bryanthansen absenceofspecificchlamydiatrachomatisinclusionmembraneproteinstriggersprematureinclusionmembranelysisandhostcelldeath AT forresthhoyt absenceofspecificchlamydiatrachomatisinclusionmembraneproteinstriggersprematureinclusionmembranelysisandhostcelldeath AT aaronbcarmody absenceofspecificchlamydiatrachomatisinclusionmembraneproteinstriggersprematureinclusionmembranelysisandhostcelldeath AT gaillsturdevant absenceofspecificchlamydiatrachomatisinclusionmembraneproteinstriggersprematureinclusionmembranelysisandhostcelldeath AT tedhackstadt absenceofspecificchlamydiatrachomatisinclusionmembraneproteinstriggersprematureinclusionmembranelysisandhostcelldeath |
_version_ |
1726001461009055744 |