Identification of a chlamydial protease-like activity factor responsible for the degradation of host transcription factors

Microbial pathogens have been selected for the capacity to evade or manipul ate host responses in order to survive after infection. Chlamydia, an oblig ate intracellular pathogen and the causative agent for many human diseases, can escape T lymphocyte immune recognition by degrading host transcription factors required for major histocompatibility complex (MHC) antigen expres sion. We have now identified a chlamydial protease- or proteasome-like acti vity factor (CPAF) that is secreted into the host cell cytosol and that is both necessary and sufficient for the degradation of host transcription fac tors RFX5 and upstream stimulation factor 1 (USF-1). The CPAF gene is highl y conserved among chlamydial strains, but has no significant overall homolo gy with other known genes. Thus, CPAF represents a unique secreted protein produced by an obligate intracellular bacterial pathogen to interfere with effective host adaptive immunity.