Fu Tongtong, Fan Zheng, Li Yujie, Li Zhoufei, Du Bing, Liu Shiyu, Cui Xiaohu, Zhang Rui, Zhao Hanqing, Feng Yanling, Xue Guanhua, Cui Jinghua, Yan Chao, Gan Lin, Feng Junxia, Xu Ziying, Yu Zihui, Tian Ziyan, Ding Zanbo, Chen Jinfeng, Chen Yujie, Yuan Jing
Department of Bacteriology, Capital Institute of Pediatrics, Beijing, China.
Department of Life Science and Medicine, University of Science and Technology of China, Hefei, China.
Front Microbiol. 2023 Feb 24;14:1106340. doi: 10.3389/fmicb.2023.1106340. eCollection 2023.
is an opportunistic pathogen that shows a unique ability to quickly respond to a variety of antibiotics. The Crp/Fnr family transcriptional regulator ArcR controls expression of arginine deiminase pathway genes , which enable the utilization of arginine as an energy source for cell growth under anaerobic conditions. However, ArcR shares low overall similarity with other Crp/Fnr family proteins, suggesting that they differ in the response to environmental stress. In this study, MIC and survival assays were performed to determine the role of ArcR in antibiotic resistance and tolerance. The results showed that deletion of reduced tolerance of to fluoroquinolone antibiotics, mainly through a defect in the response to oxidative stress. In mutant, the expression of the major catalase gene was downregulated, and overexpression restored bacterial resistance to oxidative stress and antibiotics. We showed that ArcR directly regulated transcription by binding to the promoter region of . Therefore, our results revealed the contribution of ArcR in bacterial tolerance to oxidative stress and subsequently to fluoroquinolones antibiotics. This study added our understanding on the role of Crp/Fnr family in bacterial susceptibility to antibiotics.
是一种机会致病菌，具有对多种抗生素快速作出反应的独特能力。Crp/Fnr家族转录调节因子ArcR控制精氨酸脱亚氨酶途径基因的表达，该途径能使细菌在厌氧条件下利用精氨酸作为细胞生长的能量来源。然而，ArcR与其他Crp/Fnr家族蛋白的整体相似性较低，这表明它们在对环境压力的反应上存在差异。在本研究中，进行了最低抑菌浓度（MIC）和存活试验，以确定ArcR在抗生素抗性和耐受性中的作用。结果表明，缺失ArcR会降低细菌对氟喹诺酮类抗生素的耐受性，主要是由于对氧化应激反应存在缺陷。在ArcR突变体中，主要过氧化氢酶基因的表达下调，而过表达该基因可恢复细菌对氧化应激和抗生素的抗性。我们发现ArcR通过结合该基因的启动子区域直接调控其转录。因此，我们的结果揭示了ArcR在细菌对氧化应激以及随后对氟喹诺酮类抗生素耐受性中的作用。这项研究增进了我们对Crp/Fnr家族在细菌对抗生素敏感性中作用的理解。
