Obligate intracellular pathogens, such as Chlamydia, reside and replicate in the relative safety of cytoplasmic vesicles. But infected cells often burst this cytoplasmic bubble by committing altruistic suicide through the induction of apoptosis. Now, a recent study in the Journal of Experimental Medicine shows that Chlamydia can inhibit this programmed cell death by eliminating pro-apoptotic proteins.

To investigate the molecular mechanisms used by Chlamydia to modulate apoptosis, Georg Häcker and colleagues exposed both Chlamydia-infected and uninfected human cells to UV irradiation. UV irradiation activates pro-apoptotic proteins such as BIM, which in turn activates BAX and BAK. The pathway culminates with the release of cytochrome c from the mitochondria and the induction of the deadly caspase cascade.

As expected, cells that had been infected with Chlamydia were protected against UV-induced apoptosis. Importantly, cytochrome c was retained in the mitochondria in these cells, in contrast to control cells, which showed cytosolic staining with anti-cytochrome-c antibodies. Infected cells had normal amounts of BAX/BAK protein — the mediators of cytochrome-c release — but the level of activated protein was reduced.

So, Fischer et al. turned their attention to the BH3-only protein BIM, and made the startling discovery that, despite normal expression of BIM mRNA, the protein had “almost completely disappeared from Chlamydia-infected cells”. The same was true for two other BH3-only proteins, PUMA and BAD, and experiments using a proteolytic inhibitor implicated the proteosome as the agent of destruction.

In normal cells, BIM is protected from activation by sequestration to the cytoskeleton, and disruption of cellular architecture by intracellular infection might release the protein and induce apoptosis. By destroying BIM, Chlamydia prevents host-cell death, thereby ensuring its own survival.