Characterization of Serine Hydrolases Across Clinical Isolates of Commensal Skin Bacteria Staphylococcus epidermidis Using Activity-Based Protein Profiling

The bacterial genus Staphylococcus 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 Staphylococcus aureus, 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 Staphylococcus epidermidis. Two of the S. aureus Fph enzymes were not identified in S. epidermidis. Using ABPP, we identified several candidate hydrolases that were
not previously identified in S. aureus that
may be functionally related to the Fphs. Interestingly, the activity
of the Fphs vary across clinical isolates of S. epidermidis. Biochemical characterization of the FphB homologue in S. epidermidis (SeFphB) suggests it is a functional homologue of FphB in S. aureus, but our preliminary studies suggest it may
not have a role in colonization in vivo. This potential
difference in biological function between the Fphs of closely related
staphylococcal species may provide mechanisms for specific inhibition
of S. aureus infection without perturbing commensal
communities of related bacteria.

细菌属Staphylococcus包含多种物种，它们作为共生菌定植于皮肤，但也可引起感染。先前研究在致病菌金黄色葡萄球菌（Staphylococcus aureus）中鉴定出一种被称为氟磷酸酯结合水解酶（Fphs）的丝氨酸水解酶家族，其中之一FphB充当致病因素。通过结合生物信息学和基于活性的蛋白质谱分析（ABPP），我们在相关共生菌表皮葡萄球菌（Staphylococcus epidermidis）中鉴定出这些酶的同源物。在表皮葡萄球菌中未发现金黄色葡萄球菌中的两种Fph酶。通过ABPP，我们鉴定出几种候选水解酶，这些水解酶在金黄色葡萄球菌中尚未被发现，且可能与Fphs具有功能相关性。有趣的是，Fphs的活性在表皮葡萄球菌的临床分离株中存在差异。对表皮葡萄球菌中的FphB同源物（SeFphB）进行生化特性分析表明，它可能是金黄色葡萄球菌中FphB的功能性同源物，但我们的初步研究表明，它可能在体内定植中不起作用。这种在密切相关的葡萄球菌物种之间潜在的功能差异，可能为特异性抑制金黄色葡萄球菌感染提供了机制，而不会干扰相关细菌的共生群落。