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Function, molecular mechanisms, and therapeutic potential of bacterial HtrA proteins: An evolving view.

ABSTRACT: Members of the high temperature requirement A (HtrA) protein family are widely distributed amongst prokaryotic and eukaryotic species. HtrA proteins have ATP-independent dual chaperone-protease activity and mediate protein quality control. Emerging evidence indicates that HtrA family members are vital for establishing infections and bacterial survival under stress conditions. Bacterial HtrA proteins are increasingly thought of as important new targets for antibacterial drug development. Recent literature suggests that HtrA protein AlgW from Pseudomonas aeruginosa has distinct structural, functional, and regulatory characteristics. The novel dual-signal activation mechanism seen in AlgW is required to modulate stress and drug responses in bacteria, prompting us to review our understanding of the many HtrA proteins found in microorganisms. Here, we describe the distribution of HtrA gene orthologues in pathogenic bacteria, discuss their structure-function relationships, outline the molecular mechanisms exhibited by different bacterial HtrA proteins in bacteria under selective pressure, and review the significance of recently developed small molecule inhibitors targeting HtrA in pathogenic bacteria.

SUBMITTER: Song Y

PROVIDER: S-EPMC8671199 | biostudies-literature |

REPOSITORIES: biostudies-literature

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