caviae GPIC organisms can infect ocular and urogenital tissues in guinea pig . selleck screening library Despite the differences in host range, tissue tropism, disease processes, all chlamydial species share similar genome sequences [8, 10, 11] and possess a common intracellular growth cycle with distinct biphasic stages . A chlamydial infection starts with the invasion of an epithelial cell by an infectious elementary body (EB). The internalized EB rapidly develops into a noninfectious but metabolically active reticulate body (RB) that undergoes multiplication. The progeny RBs then differentiate back into EBs for spreading to new cells. All chlamydial biosynthesis
activities are restricted within a cytoplasmic vacuole known as inclusion . During the intravacoular developmental ICG-001 concentration cycle, chlamydial organisms have to take up nutrients
and energy from host cells [13–16] and maintain the integrity of the host cells . To achieve these goals, chlamydial organisms have evolved the ability to secrete proteins into the inclusion membrane [18, 19] and host cell cytoplasm [17, 20, 21]. Identifying the chlamydial secretion proteins has greatly facilitated the understanding of chlamydial pathogenic mechanisms [20, 22–31]. CPAF, a chlamydial protease/proteasome-like R788 supplier activity factor that is now known as a serine protease [32, 33], was found to secrete into host cell cytosol more than a decade ago . CPAF can degrade a wide array of host proteins including cytokeratins for facilitating chlamydial inclusion expansion
[34–36], second transcriptional factors required for MHC antigen expression for evading immune detection [37, 38] and BH3-only domain proteins for blocking apoptosis [39, 40]. Another example of chlamydia-secreted proteins is the chlamydial tail-specific protease that has been found to dampen the inflammatory responses by cleaving host NF-κB molecules [41, 42]. These observations have led to the hypothesis that Chlamydia may have evolved a proteolysis strategy for manipulating host cell signaling pathways . Among the several dozens of putative proteases encoded by chlamydial genomes [11, 43], the chlamydial HtrA (cHtrA) is a most conserved protease. HtrA from eukaryotic and prokaryotic species exhibits both chaperone and proteolytic activities [44, 45] with a broad proteolytic substrate specificity [44, 45]. HtrA is a hexamer formed by staggered association of trimeric rings and access to the proteolytic sites in central cavity is controlled by 12 PDZ domains in the sidewall [46, 47]. In eukaryotic cells, HtrA responds to unfolded proteins in the endoplasmic reticulum (ER) by cleaving and releasing the ER membrane-anchored transcription factors ATF6 and SREBP into nucleus to activate the expression of proteins required for the unfolded protein response and cholesterol biosynthesis [48, 49].