Ruo-Yi Xue1, Chang Liu1, Qing-Tao Xiao2, Si Sun1, Quan-Ming Zou3, Hai-Bo Li4. 1. National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, PR China. 2. College of Psychology, Third Military Medical University, Chongqing, PR China. 3. National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, PR China. Electronic address: qmzou2007@163.com. 4. National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, PR China. Electronic address: lihaibo@tmmu.edu.cn.
Abstract
BACKGROUND: 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. OBJECTIVES: 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. SOURCES: A search of PubMed was performed to identify relevant studies. CONTENT: 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. IMPLICATIONS: 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.
BACKGROUND: 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. OBJECTIVES: 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. SOURCES: A search of PubMed was performed to identify relevant studies. CONTENT: 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. IMPLICATIONS: 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.