High temperature requirement A (HtrA) protease (HtrA)

High temperature requirement A (HtrA) is a secreted serine protease and chaperone produced by Helicobacter pylori that plays a critical role in bacterial pathogenesis and host cell invasion (Löwer et al., 2011). It functions by cleaving key host cell-cell adhesion proteins, most notably E-cadherin, as well as occludin and claudin-8, which leads to the disruption of the gastric epithelial barrier (Tegtmeyer et al., 2017). This proteolytic activity facilitates the deep penetration of H. pylori into the gastric mucosa and enables the delivery of virulence factors like CagA into host cells, promoting chronic inflammation. HtrA is considered a promising therapeutic target because its inhibition can prevent bacterial transmigration and the subsequent development of severe conditions such as peptic ulcers and gastric cancer (Harrer et al., 2017). Several small-molecule inhibitors, including the lead compound JO146 and natural products like Fisetin and Quercetin, have been identified in preclinical studies to block HtrA's proteolytic activity and reduce bacterial virulence (Li Gao et al., 2025).

Other names

HpHtrASerine protease HtrADegP homologHigh temperature requirement AH. pylori HtrA

Inhibition of the HtrA serine protease activity to prevent the cleavage of host cell adhesion proteins (e.g., E-cadherin), thereby blocking bacterial invasion and transmigration.