Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China; Department of Analytical Chemistry and CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Department of Analytical Chemistry and CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
J Proteomics. 2020 Aug 30;226:103900. doi: 10.1016/j.jprot.2020.103900. Epub 2020 Jul 22.
Staphylococcus epidermidis is a common causative of nosocomial infections associated with indwelling medical devices. To date, the mechanisms of the pathogenicity and drug resistance of S. epidermidis have not been clearly elucidated. AbfR has been previously identified as an oxidation-sensing regulator that regulates bacterial aggregation and biofilm formation by responding to oxidative stress in S. epidermidis; however, the regulatory pathways of AbfR are underexplored. In this study, we investigated the oxidation-sensing regulatory mechanism of AbfR using TMT10-plex labelling quantitative proteomic and untargeted metabolomic approaches. Integrated analysis of two omics datasets indicated that abfR depletion influenced nucleic acid metabolism and activated the DNA mismatch repair pathway. In addition, several energy-related metabolic pathways, including tricarboxylic acid (TCA) cycle, glycolysis, and arginine metabolism, were remarkably impacted by the deletion of abfR. This study revealed the regulatory networks of the transcription factor AbfR from a multi-omics view and demonstrated that AbfR played a broad role in not only mismatch repair but also energy metabolism, enabling S. epidermidis to constantly sense and adapt to environmental stress. SIGNIFICANCE: Staphylococcus epidermidis has emerged as a major nosocomial infection causing pathogen. AbfR, a transcription factor of S. epidermidis, plays an important role in oxidative stress, cell aggregation, and biofilm formation; however, the regulatory mechanism of AbfR is unknown. Using proteomic and metabolomic approaches, this study unveils the global regulatory networks of AbfR, and demonstrates that AbfR not only regulates the DNA mismatch repair pathway by an oxidation sensing mechanism but also affects energy metabolism. This study expands the body of knowledge related to regulatory transcription factors in staphylococci and lays a foundation for future research on clinical infections caused by S. epidermidis.
表皮葡萄球菌是一种常见的医源性感染病原体，与留置医疗设备有关。迄今为止，表皮葡萄球菌的致病性和耐药性机制尚未得到明确阐明。AbfR 先前被鉴定为一种氧化感应调节剂，通过响应表皮葡萄球菌中的氧化应激来调节细菌聚集和生物膜形成；然而，AbfR 的调节途径尚未得到充分探索。在这项研究中，我们使用 TMT10-plex 标记定量蛋白质组学和非靶向代谢组学方法研究了 AbfR 的氧化感应调节机制。两个组学数据集的综合分析表明，abfR 缺失会影响核酸代谢并激活 DNA 错配修复途径。此外，几种与能量相关的代谢途径，包括三羧酸 (TCA) 循环、糖酵解和精氨酸代谢，也因 abfR 的缺失而受到显著影响。这项研究从多组学角度揭示了转录因子 AbfR 的调控网络，并表明 AbfR 不仅在错配修复中发挥广泛作用，而且在能量代谢中也发挥作用，使表皮葡萄球菌能够不断感知和适应环境压力。意义：表皮葡萄球菌已成为主要的医院感染病原体。表皮葡萄球菌的转录因子 AbfR 在氧化应激、细胞聚集和生物膜形成中发挥重要作用；然而，AbfR 的调节机制尚不清楚。本研究采用蛋白质组学和代谢组学方法揭示了 AbfR 的全局调控网络，并表明 AbfR 不仅通过氧化感应机制调节 DNA 错配修复途径，还影响能量代谢。这项研究扩展了关于葡萄球菌调节转录因子的知识体系，为未来研究表皮葡萄球菌引起的临床感染奠定了基础。
