Journal article
Laser-mediated rupture of chlamydial inclusions triggers pathogen egress and host cell necrosis
MC Kerr, GA Gomez, C Ferguson, MC Tanzer, JM Murphy, AS Yap, RG Parton, WM Huston, RD Teasdale
Nature Communications | NATURE PUBLISHING GROUP | Published : 2017
DOI: 10.1038/ncomms14729
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 ca..
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Awarded by National Health and Medical Research Council
Funding Acknowledgements
This work was supported by funding from the National Health and Medical Research Council (NHMRC) of Australia (606788, APP1105754, APP1044041, APP569542, APP1041929, APP1037320, APP1067405, 9000220), Victorian Government Operational Infrastructure Support schemes and the Australian Research Council (DP150100364). M.C.K. was supported by an Australian Research Council Discovery Early Career Researcher Award (DE120102321) and M.C.T. was supported by a Victorian International Research Scholarship. We acknowledge the facilities and the scientific and technical assistance of the Australian Microscopy & Microanalysis Research Facility, UQ and the Australian Cancer Research Foundation (ACRF)/Institute for Molecular Bioscience (IMB) Dynamic Imaging Facility for Cancer Biology. Finally, we thank David Segal, David Huang, John Silke and Marco Herold (The Walter and Eliza Hall Institute of Medical Research, Australia) for reagents and helpful discussions in the preparation of this manuscript.