Chlamydial membrane vesicles deliver the chlamydial porin OmpA to mitochondria to inhibit apoptosis

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Summary Chlamydiae are obligate intracellular bacteria that inhibit mitochondrial apoptosis to maintain integrity of the host cell. We have previously reported that a chlamydial outer membrane β-barrel protein, the porin OmpA, can during ectopic expression inhibit mitochondrial apoptosis through direct interaction with the BCL-2-family effectors BAX and BAK. We here show that OmpA from Chlamydia trachomatis ( Ctr ) uses membrane vesicles for its delivery to the outer mitochondrial membrane during Ctr infection. Using a number of imaging and fractionation techniques, we show that OmpA during infection reaches mitochondria and is inserted into mitochondrial membranes. Purified membrane vesicles (MV) from Ctr -infected cells contained OmpA. When added to uninfected cells, MV fused with mitochondrial membranes, causing the interaction of OmpA with BAK and the cytosolic retro-translocation of BAX. MV addition to uninfected cells protected the cells against apoptosis. We propose a structural model of this BAK inhibition by OmpA that reenacts the inhibition of BAK by the mitochondrial porin VDAC2. The results provide evidence that the porin from Chlamydia , as well as the structurally similar porin from the related Simkania , specifically exploits its relationship to mitochondrial porins to protect the infected cell against apoptosis and to enable intracellular growth of the bacteria in human cells.

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