benzyloxycarbonylvalyl-alanyl-aspartyl-fluoromethyl-ketone and Conjunctivitis--Inclusion

Infection with an obligate intracellular bacterium, the Chlamydia trachomatis lymphogranuloma venereum (LGV/L2) strain or the guinea pig inclusion conjunctivitis serovar of Chlamydia psittaci, leads to apoptosis of host cells. The apoptosis is not affected by a broad-spectrum caspase inhibitor, and caspase-3 is not activated in infected cells, suggesting that apoptosis mediated by these two strains of Chlamydia is independent of known caspases. Overexpression of the proapoptotic Bcl-2 family member, Bax, was previously shown to induce caspase-independent apoptosis, and we find that Bax is activated and translocates from the cytosol to the mitochondria in C. psittaci-infected cells. C. psittaci-induced apoptosis is inhibited in host cells overexpressing Bax inhibitor-1 and is inhibited through overexpression of Bcl-2, which blocks both caspase-dependent and -independent apoptosis. As Bax and mitochondria are ideally located to sense stress-related metabolic changes emanating from the interior of an infected cell, it is likely that Bax-dependent apoptosis may also be observed in cells infected with other intracellular pathogens.

Topics: Amino Acid Chloromethyl Ketones; Apoptosis; Apoptosis Regulatory Proteins; bcl-2-Associated X Protein; Caspase Inhibitors; Chlamydia trachomatis; Chlamydophila psittaci; Conjunctivitis, Inclusion; Cysteine Proteinase Inhibitors; HeLa Cells; Humans; Lymphogranuloma Venereum; Membrane Proteins; Proteins; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-bcl-2; U937 Cells