Inhibition of Apoptosis in Chlamydia-infected Cells: Blockade of Mitochondrial Cytochrome c Release and Caspase Activation

Abstract

We report that chlamydiae, which are obligate intracellular bacterial pathogens, possess a novel antiapoptotic mechanism. Chlamydia-infected host cells are profoundly resistant to apoptosis induced by a wide spectrum of proapoptotic stimuli including the kinase inhibitor staurosporine, the DNA-damaging agent etoposide, and several immunological apoptosis-inducing molecules such as tumor necrosis factor-α, Fas antibody, and granzyme B/perforin. The antiapoptotic activity was dependent on chlamydial but not host protein synthesis. These observations suggest that chlamydia may encode factors that interrupt many different host cell apoptotic pathways. We found that activation of the downstream caspase 3 and cleavage of poly (ADP-ribose) polymerase were inhibited in chlamydia-infected cells. Mitochondrial cytochrome c release into the cytosol induced by proapoptotic factors was also prevented by chlamydial infection. These observations suggest that chlamydial proteins may interrupt diverse apoptotic pathways by blocking mitochondrial cytochrome c release, a central step proposed to convert the upstream private pathways into an effector apoptotic pathway for amplification of downstream caspases. Thus, we have identified a chlamydial antiapoptosis mechanism(s) that will help define chlamydial pathogenesis and may also provide information about the central mechanisms regulating host cell apoptosis.

Coinfection with Mycoplasma Pneumoniae and Chlamydia Pneumoniae in ruptured plaques associated with acute myocardial infarction

“…On the other hand, a recent study 73 has shown that chlamydial infection inhibits apoptosis in the host cell. Therefore, the presence of infection with chlamydia and mycoplasma may explain the proliferation of smooth muscle cells and the fact of their monoclonality 74,75 in atherosclerotic plaques.…”

Genome-wide genetic investigation of serological measures of common infections

“…21 Although the mechanism by which infection with C. pneumoniae may increase the risk of lung cancer is not known, one possible explanation is that it may induce irregular apoptosis in tissues. 22 The human SRSF6 protein has also been linked to infection with HIV-1, reportedly regulating HIV-1 mRNA processing and possibly being involved in nuclear export of spliced mRNAs. 23,24 L3MBTL1, on the other hand, is a tumor suppressor gene that appears to suppress genes and microRNAs that re-activate during tumor growth and whose expression is associated with decreased risk of death due to breast cancer.…”

Chlamydia trachomatis Infection Induces Cleavage of the Mitotic Cyclin B1

“…Most importantly, the cell must remain viable during infection. C. trachomatis has been shown to promote host cell survival by actively inhibiting the mitochondrial pathway of apoptosis, in part by triggering proteasomal degradation of proapoptotic factors within the cell (8,(10)(11)(12)41). Even host cell division may pose challenges to C. trachomatis replication, since important nutrients may be consumed as the cell divides.…”