Laser-mediated rupture of chlamydial inclusions triggers pathogen egress and host cell necrosis

Kerr, Markus C., Gomez, Guillermo A., Ferguson, Charles, Tanzer, Maria C., Murphy, James M., Yap, Alpha S., Parton, Robert G., Huston, Wilhelmina M. and Teasdale, Rohan D. (2017) Laser-mediated rupture of chlamydial inclusions triggers pathogen egress and host cell necrosis. Nature Communications, 8 14729. doi:10.1038/ncomms14729


Author Kerr, Markus C.
Gomez, Guillermo A.
Ferguson, Charles
Tanzer, Maria C.
Murphy, James M.
Yap, Alpha S.
Parton, Robert G.
Huston, Wilhelmina M.
Teasdale, Rohan D.
Title Laser-mediated rupture of chlamydial inclusions triggers pathogen egress and host cell necrosis
Journal name Nature Communications   Check publisher's open access policy
ISSN 2041-1723
Publication date 2017-03-10
Year available 2017
Sub-type Article (original research)
DOI 10.1038/ncomms14729
Open Access Status DOI
Volume 8
Start page 14729
Total pages 12
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Subject 1600 Chemistry
1300 Biochemistry, Genetics and Molecular Biology
3100 Physics and Astronomy
Abstract Remarkably little is known about how intracellular pathogens exit the host cell in order to infect new hosts. Pathogenic chlamydiae egress by first rupturing their replicative niche (the inclusion) before rapidly lysing the host cell. Here we apply a laser ablation strategy to specifically disrupt the chlamydial inclusion, thereby uncoupling inclusion rupture from the subsequent cell lysis and allowing us to dissect the molecular events involved in each step. Pharmacological inhibition of host cell calpains inhibits inclusion rupture, but not subsequent cell lysis. Further, we demonstrate that inclusion rupture triggers a rapid necrotic cell death pathway independent of BAK, BAX, RIP1 and caspases. Both processes work sequentially to efficiently liberate the pathogen from the host cytoplasm, promoting secondary infection. These results reconcile the pathogen's known capacity to promote host cell survival and induce cell death.
Keyword Multidisciplinary Sciences
Science & Technology - Other Topics
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID 606788
DP150100364
DE120102321
Institutional Status UQ

 
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