The disulfide bond (DSB) forming system and in particular DsbA, is a key bacterial oxidative folding catalyst. Due to its role in promoting the correct assembly of a wide range of virulence factors required at different stages of the infection process, DsbA is a master virulence rheostat, making it an attractive target for the development of new virulence blockers. Although DSB systems have been extensively studied across different bacterial species, to date, little is known about how DsbA oxidoreductases are able to recognize and interact with such a wide range of substrates. This review summarizes the current knowledge on the DsbA enzymes, with special attention on their interaction with the partner oxidase DsbB and substrates associated with bacterial virulence. The structurally and functionally diverse set of bacterial proteins that rely on DsbA-mediated disulfide bond formation are summarized. Local sequence and secondary structure elements of these substrates are analyzed to identify common elements recognized by DsbA enzymes. This not only provides information on protein folding systems in bacteria but also offers tools for identifying new DsbA substrates and informs current efforts aimed at developing DsbA targeted anti-microbials.

二硫键 (DSB) 形成系统，尤其是 DsbA，是关键的细菌氧化折叠催化剂。由于其在促进感染过程不同阶段所需的各种毒力因子的正确组装方面的作用，DsbA 是一种主要的毒力变阻器，使其成为开发新毒力阻滞剂的有吸引力的目标。尽管 DSB 系统已在不同的细菌物种中得到广泛研究，但迄今为止，人们对 DsbA 氧化还原酶如何能够识别如此广泛的底物并与之相互作用知之甚少。本综述总结了 DsbA 酶的当前知识，特别关注它们与伙伴氧化酶 DsbB 和与细菌毒力相关的底物的相互作用。总结了依赖 DsbA 介导的二硫键形成的结构和功能多样的细菌蛋白质组。分析这些底物的局部序列和二级结构元素以鉴定 DsbA 酶识别的常见元素。这不仅提供了有关细菌蛋白质折叠系统的信息，而且还提供了用于识别新 DsbA 底物的工具，并为目前旨在开发 DsbA 靶向抗微生物剂的努力提供信息。