Li Tian, Gao Yiwen, Zhang Xiaoyue, Zhao Yuxiao, Hu Fuyao, Li Wei, Li Lixiang, Pan Hongwei, Zhang Yi, Chen Ying
Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, China.
Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, China.
Commun Biol. 2025 Apr 9;8(1):586. doi: 10.1038/s42003-025-07996-y.
Bergeyella cardium causes infections in human organs. However, the mechanism of the virulence of B. cardium is unclear. Peptidases are important virulence factors in bacterial pathogens. Here, we identified three KP-43 subfamily peptidases, SpBcA, SpBcB and SpBcC, which are putative T9SS cargo proteins, and analyzed their protease activity. SpBcA and SpBcB are active in vitro and contain a propeptide that passes through the active site of the S8 peptidase domain and inhibits its activity. SpBcA activates itself by cleaving the propeptide at N102 within the TSNA (100-103) peptide and a putative cleavage site at 116-120 (TSPGL). Additionally, SpBcA degrades host defense molecules, fibrinogen, antimicrobial peptide LL-37 and gelatin in vitro and induces cell death in vivo, suggesting its role as a virulence factor. This study revealed the self-cleavage regulatory mechanism of SpBcA and provided a basis for studying how B. cardium uses peptidases as virulence factors in vivo.
贲门伯格菌可引起人体器官感染。然而，贲门伯格菌的毒力机制尚不清楚。肽酶是细菌病原体中的重要毒力因子。在此，我们鉴定出三种KP - 43亚家族肽酶，SpBcA、SpBcB和SpBcC，它们是假定的T9SS货物蛋白，并分析了它们的蛋白酶活性。SpBcA和SpBcB在体外具有活性，且含有一个前肽，该前肽穿过S8肽酶结构域的活性位点并抑制其活性。SpBcA通过在TSNA（100 - 103）肽内的N102以及116 - 120（TSPGL）处的假定切割位点切割前肽来自我激活。此外，SpBcA在体外可降解宿主防御分子、纤维蛋白原、抗菌肽LL - 37和明胶，并在体内诱导细胞死亡，表明其作为毒力因子的作用。本研究揭示了SpBcA的自我切割调节机制，并为研究贲门伯格菌如何在体内将肽酶用作毒力因子提供了基础。
