bacterial pathogenesis: cheating death
TRANSCRIPT
NATURE REVIEWS | MICROBIOLOGY VOLUME 2 | DECEMBER 2004 | 1
Obligate intracellular pathogens, suchas Chlamydia, reside and replicate inthe relative safety of cytoplasmic vesi-cles. But infected cells often burst thiscytoplasmic bubble by committingaltruistic suicide through the induc-tion of apoptosis. Now, a recent studyin the Journal of ExperimentalMedicine shows that Chlamydia caninhibit this programmed cell death byeliminating pro-apoptotic proteins.
To investigate the molecularmechanisms used by Chlamydia tomodulate apoptosis, Georg Häckerand colleagues exposed bothChlamydia-infected and uninfectedhuman cells to UV irradiation. UVirradiation activates pro-apoptoticproteins such as BIM, which in turnactivates BAX and BAK. The pathwayculminates with the release ofcytochrome c from the mitochondriaand the induction of the deadly cas-pase cascade.
As expected, cells that had beeninfected with Chlamydia were pro-tected against UV-induced apoptosis.Importantly, cytochrome c wasretained in the mitochondria in thesecells, in contrast to control cells,which showed cytosolic staining withanti-cytochrome-c antibodies.Infected cells had normal amounts ofBAX/BAK protein — the mediatorsof cytochrome-c release — but thelevel of activated protein wasreduced.
So, Fischer et al. turned theirattention to the BH3-only proteinBIM, and made the startling discov-ery that, despite normal expression of
BIM mRNA, the protein had “almostcompletely disappeared fromChlamydia-infected cells”. The samewas true for two other BH3-only pro-teins, PUMA and BAD, and experi-ments using a proteolytic inhibitorimplicated the proteosome as theagent of destruction.
In normal cells, BIM is protectedfrom activation by sequestration tothe cytoskeleton, and disruption ofcellular architecture by intracellularinfection might release the proteinand induce apoptosis. By destroyingBIM, Chlamydia prevents host-celldeath, thereby ensuring its own sur-vival.
Shannon AmoilsReferences and links
ORIGINAL RESEARCH PAPER Fischer, S. F. etal. Chlamydia inhibit host cell apoptosis bydegradation of proapoptotic BH3-only proteins. J.Exp. Med. 200, 905–916 (2004) FURTHER READING Byrne, G. I. & Ojcius D. M.Chlamydia and apoptosis: life and death decisionsof an intracellular pathogen. Nature Rev. Microbiol.2, 802–808 (2004)
Cheating death
B A C T E R I A L PAT H O G E N E S I S
RESEARCH
HIGHLIGHTS
URLS for online linksSwiss-Prot http://us.expasy.org/sprot/BADhttp://us.expasy.org/cgi-bin/niceprot.pl?Q92934BAKhttp://us.expasy.org/cgi-bin/niceprot.pl?Q16611BIMhttp://us.expasy.org/cgi-bin/niceprot.pl?O43521
Entrez:http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene BAXhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=581