Department of Bioengineering and ChEM-H, Stanford University, Stanford, California 94305, United States.
Dermatology Service, Veterans Affairs Medical Center, San Francisco, California 94121, United States.
ACS Infect Dis. 2020 May 8;6(5):930-938. doi: 10.1021/acsinfecdis.0c00095. Epub 2020 Apr 27.
The bacterial genus comprises diverse species that colonize the skin as commensals but can also cause infection. Previous work identified a family of serine hydrolases termed fluorophoshonate-binding hydrolases (Fphs) in the pathogenic bacteria , one of which, FphB, functions as a virulence factor. Using a combination of bioinformatics and activity-based protein profiling (ABPP), we identify homologues of these enzymes in the related commensal bacteria . Two of the Fph enzymes were not identified in . Using ABPP, we identified several candidate hydrolases that were not previously identified in that may be functionally related to the Fphs. Interestingly, the activity of the Fphs vary across clinical isolates of . Biochemical characterization of the FphB homologue in (SeFphB) suggests it is a functional homologue of FphB in , but our preliminary studies suggest it may not have a role in colonization . This potential difference in biological function between the Fphs of closely related staphylococcal species may provide mechanisms for specific inhibition of infection without perturbing commensal communities of related bacteria.
包含多种定植于皮肤表面的共生菌，但也能引起感染的细菌属。先前的研究在病原菌 中鉴定出一类丝氨酸水解酶，称为氟膦酸盐结合水解酶（Fphs），其中一种酶 FphB 是一种毒力因子。我们结合生物信息学和基于活性的蛋白质谱分析（ABPP），在相关的共生菌 中鉴定出这些酶的同源物。 中的两种 Fph 酶未被鉴定出来。使用 ABPP，我们鉴定出了几种以前在 中未被鉴定出的候选水解酶，它们可能与 Fphs 在功能上有关。有趣的是，Fphs 的活性在 的临床分离株中存在差异。 中 FphB 同源物（SeFphB）的生化特征表明它是 FphB 在 中的功能同源物，但我们的初步研究表明它在定植中可能没有作用。密切相关的葡萄球菌种的 Fphs 之间这种潜在的生物学功能差异可能为特异性抑制 感染而不扰乱相关细菌的共生群落提供了机制。
