HtrA family proteases of bacterial pathogens: pros and cons for their therapeutic use

Abstract

BackgroundBecause there is an urgent need to develop antibacterial therapies other than antibiotics, research has increasingly focused on the high-temperature-requirement protein A (HtrA) family proteases, which have both serine protease and chaperone activities. ObjectivesThe research progresses of the role of HtrA family proteases in the pathogenesis of bacterial infections are summarized, and the pros and cons of exploiting HtrA inhibitors in antibacterial drug development are proposed. SourcesA search of PubMed was performed to identify relevant studies. ContentHtrA is essential for bacteria to survive in harsh environments, based on the degradation and refolding of misfolded proteins. Moreover, HtrA family protease can lyse the epithelial cell barrier to promote invasion and can also act as or assist virulence factors to enhance pathogenicity. On the other hand, HtrA secreted by certain bacteria can also affect intra- and interspecies biofilm formation (the mechanism of its promotion or inhibition has not yet been proven). Overall, in view of the role of the HtrA family in promoting bacterial pathogenicity, effective HtrA inhibitors may be an exciting direction for drug development. Therefore, the research progress regarding HtrA inhibitors are summarized and the risks of their application are discussed. ImplicationsThis review will be useful both for investigators involved in the HtrA field as well as those wishing to acquire a basic understanding of the role and potential implementations of HtrA.