Department of Biochemistry, Central University of Rajasthan, Ajmer 305817, India.
Department of Biochemistry, Central University of Rajasthan, Ajmer 305817, India.
Int J Biol Macromol. 2022 Sep 30;217:931-943. doi: 10.1016/j.ijbiomac.2022.07.176. Epub 2022 Jul 26.
Antibiotics have a primary mode of actions, and most of them have a common secondary mode of action via reactive species (ROS and RNS) mediated DNA damage. Bacteria have been able to tolerate this DNA damage by SOS (Save-Our-Soul) response. RecA is the universal essential key protein of the DNA damage mediated SOS repair in various bacteria including ESKAPE pathogens. In addition, antibiotics also triggers activation of various other bacterial mechanisms such as biofilm formation, host dependent responses, persister subpopulation formation. These supporting the survival of bacteria in unfriendly natural conditions i.e. antibiotic presence. This review highlights the detailed mechanism of RecA mediated SOS response as well as role of RecA-LexA interaction in SOS response. The review also focuses on inter-connection between DNA damage repair pathway (like SOS response) with other survival mechanisms of bacteria such as host mediated RecA induction, persister-SOS interplay, and biofilm-SOS interplay. This understanding of inter-connection of SOS response with different other survival mechanisms will prove beneficial in targeting the SOS response for prevention and development of therapeutics against recalcitrant bacterial infections. The review also covers the significance of RecA as a promising potent therapeutic target for hindering bacterial SOS response in prevailing successful treatments of bacterial infections and enhancing the conventional antibiotic efficiency.
抗生素具有主要作用模式，其中大多数通过活性氧 (ROS) 和活性氮 (RNS) 介导的 DNA 损伤具有共同的次要作用模式。细菌通过 SOS（拯救灵魂）反应能够耐受这种 DNA 损伤。RecA 是包括 ESKAPE 病原体在内的各种细菌中 DNA 损伤介导的 SOS 修复的普遍必需关键蛋白。此外，抗生素还会触发各种其他细菌机制的激活，例如生物膜形成、宿主依赖性反应、持久亚群形成。这些机制支持细菌在不利的自然条件下生存，即在抗生素存在的情况下。本综述重点介绍了 RecA 介导的 SOS 反应的详细机制以及 RecA-LexA 相互作用在 SOS 反应中的作用。该综述还侧重于 DNA 损伤修复途径（如 SOS 反应）与细菌其他生存机制（如宿主介导的 RecA 诱导、持久菌-SOS 相互作用和生物膜-SOS 相互作用）之间的联系。了解 SOS 反应与不同其他生存机制的联系将有助于针对 SOS 反应进行靶向治疗，以预防和开发针对顽固性细菌感染的治疗方法。该综述还涵盖了 RecA 作为一种有前途的有效治疗靶点的重要性，用于阻止细菌 SOS 反应，从而成功治疗细菌感染并提高传统抗生素的效率。
