Laser-mediated rupture of chlamydial inclusions triggers pathogen egress and host cell necrosis
- Author(s)
- Kerr, MC; Gomez, GA; Ferguson, C; Tanzer, MC; Murphy, JM; Yap, AS; Parton, RG; Huston, WM; Teasdale, RD;
- Journal Title
- Nat Commun
- Publication Type
- Journal Article
- 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.
- Publisher
- Springer Nature
- Research Division(s)
- Cell Signalling And Cell Death
- PubMed ID
- 28281536
- Publisher's Version
- https://doi.org/10.1038/ncomms14729
- Open Access at Publisher's Site
https://www-nature-com/articles/ncomms14729- NHMRC Grants
- NHMRC/606788, NHMRC/1105754, NHMRC/1044041, NHMRC/569542, NHMRC/1041929, NHMRC/1037320, NHMRC/1067405,
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2017-04-12 10:42:09
Last Modified: 2017-04-12 11:00:14