Periplasmic serine endoprotease DegP-like (HtrA) (CtHtrA)

Chlamydia trachomatis HtrA (CtHtrA) is a periplasmic serine protease and molecular chaperone that is essential for the survival and replication of the obligate intracellular bacterium Chlamydia trachomatis (UniProt P18584; PubMed: 24392355). It belongs to the High temperature requirement A (HtrA) family, characterized by a chymotrypsin-like protease domain and PDZ domains that regulate its activity (PubMed: 31362144). CtHtrA performs a dual function: it facilitates the proper folding of outer membrane proteins and degrades misfolded or denatured proteins that accumulate during environmental stress, such as heat shock or antibiotic treatment (PubMed: 24392355). The protein is critical during the mid-replicative phase of the chlamydial developmental cycle, and its inhibition leads to the loss of chlamydial inclusions and failure to produce infectious elementary bodies (PubMed: 24392355). Consequently, CtHtrA is a promising therapeutic target for treating chlamydial infections, which are major causes of sexually transmitted diseases and preventable blindness (trachoma) (PubMed: 31362144). Experimental inhibitors like the tripeptide JO146 and various isocoumarin derivatives have shown potent anti-chlamydial activity by targeting this enzyme (PubMed: 31362144; PubMed: 31521657). However, achieving selectivity over human HtrA homologs and other host serine proteases remains a significant challenge in drug development (PubMed: 31362144).

Other names

59 kDa immunogenic proteinProtease DoSK59DegPHigh temperature requirement ACtHtrACT823CTL0195

Inhibition of the serine protease and chaperone activities of HtrA, leading to the accumulation of misfolded proteins and arrest of the chlamydial developmental cycle (PubMed: 24392355, 31362144).