National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, PR China.
College of Psychology, Third Military Medical University, Chongqing, PR China.
Clin Microbiol Infect. 2021 Apr;27(4):559-564. doi: 10.1016/j.cmi.2020.12.017. Epub 2021 Jan 5.
Because 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.
The 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.
A search of PubMed was performed to identify relevant studies.
HtrA 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.
This 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.
由于急需开发抗生素以外的抗菌疗法，研究越来越集中于高温需求蛋白 A（HtrA）家族蛋白酶，其具有丝氨酸蛋白酶和伴侣活性。
总结 HtrA 家族蛋白酶在细菌感染发病机制中的作用的研究进展，并提出利用 HtrA 抑制剂开发抗菌药物的优缺点。
通过 PubMed 搜索以确定相关研究。
基于对错误折叠蛋白的降解和重折叠，HtrA 对于细菌在恶劣环境中生存是必不可少的。此外，HtrA 家族蛋白酶可裂解上皮细胞屏障以促进侵袭，还可以作为或辅助毒力因子来增强致病性。另一方面，某些细菌分泌的 HtrA 也可以影响种内和种间生物膜的形成（其促进或抑制的机制尚未得到证实）。总的来说，鉴于 HtrA 家族在促进细菌致病性方面的作用，有效的 HtrA 抑制剂可能是药物开发的一个令人兴奋的方向。因此，总结了 HtrA 抑制剂的研究进展，并讨论了其应用的风险。
本综述对于参与 HtrA 领域的研究人员以及希望基本了解 HtrA 的作用和潜在应用的人员都将是有用的。
