The human pathogen Helicobacter pylori is a major risk factor for gastric disease development. Serine protease HtrA is an important bacterial virulence factor that cleaves the cell junction proteins occludin, claudin-8 and E-cadherin, which causes gastric tissue damage. Using casein zymography, we discovered that HtrA trimer stability varies in clinical H. pylori strains. Subsequent sequence analyses revealed that HtrA trimer stability correlated with the presence of leucine or serine residue at position 171. The importance of these amino acids in determining trimer stability was confirmed by leucine-to-serine swapping experiments using isogenic H. pylori mutant strains as well as recombinant HtrA proteins. In addition, this sequence position displays a high sequence variability among various bacterial species, but generally exhibits a preference for hydrophilic amino acids. This natural L/S171 polymorphism in H. pylori may affect the protease activity of HtrA during infection, which could be of clinical importance and may determine gastric disease development.

人类病原体幽门螺杆菌是胃病发展的主要危险因素。丝氨酸蛋白酶HtrA是一种重要的细菌毒力因子，可裂解细胞连接蛋白occludin、claudin-8和E-cadherin，从而导致胃组织损伤。使用酪蛋白酶谱分析，我们发现 HtrA 三聚体稳定性在临床幽门螺杆菌菌株中存在差异。随后的序列分析表明，HtrA 三聚体稳定性与 171 位亮氨酸或丝氨酸残基的存在相关。这些氨基酸在确定三聚体稳定性中的重要性通过使用同基因幽门螺杆菌的亮氨酸到丝氨酸交换实验得到了证实突变菌株以及重组 HtrA 蛋白。此外，该序列位置在不同细菌物种之间表现出较高的序列变异性，但通常表现出对亲水性氨基酸的偏好。幽门螺杆菌中的这种天然 L/S171 多态性可能会影响感染过程中 HtrA 的蛋白酶活性，这可能具有临床重要性，并可能决定胃病的发展。