Yunnan Institute of Microbiology, Yunnan University, 2 Cui Hu Bei Lu, Kunming, Yunnan 650091, China.
J Antimicrob Chemother. 2011 Feb;66(2):323-31. doi: 10.1093/jac/dkq427. Epub 2010 Nov 23.
To explore bacterial cellular factors that protect against the lethal effect of antimicrobial stress as potential targets of antimicrobial potentiators, the role of Escherichia coli YrbB in protecting cells from quinolone-mediated cell death was studied.
A set of isogenic strains containing different mutations in stress response genes of E. coli was constructed by P1-mediated transduction. The susceptibility of these strains to the lethal action of quinolones was determined by measuring viable colony counts on agar plates after treatment with quinolones under various conditions.
A yrbB mutation rendered E. coli cells more susceptible to the lethal action of quinolones under conditions in which bacteriostatic susceptibility was unaffected. YrbB worked in both lethal pathways of quinolone action. Hydroxyl radical accumulation was required for nalidixic acid-mediated killing; however, in the absence of functional YrbB there was an additional mechanism through which nalidixic acid could kill cells independently of hydroxyl radical action. The E. coli chromosomal toxin-antitoxin system ChpB, but not the SOS system, was found to be involved in the hydroxyl radical-independent lethal mechanism. In addition, proteases ClpP and Lon were also involved in the action of YrbB. Besides quinolones, YrbB also played a protective role in cellular responses to other stressors, such as mitomycin C, ultraviolet light and hydrogen peroxide.
YrbB played a protective role in the lethal action of quinolones through a hydroxyl radical-independent and toxin-antitoxin-dependent mechanism, which makes it a potential target for antimicrobial enhancement.
探索能够抵抗抗菌药物应激致细胞死亡作用的细菌细胞因子，将其作为抗菌增效剂的潜在作用靶点。本研究旨在探讨大肠杆菌 YrbB 蛋白在保护细胞免受喹诺酮类药物致细胞死亡中的作用。
通过 P1 噬菌体转导构建了一组包含大肠杆菌不同应激反应基因突变的同源菌株。通过在不同条件下用喹诺酮类药物处理后，在琼脂平板上测定活菌数来确定这些菌株对喹诺酮类药物致细胞死亡作用的敏感性。
yrbB 基因突变使大肠杆菌细胞在抑菌药敏性不受影响的情况下，对喹诺酮类药物的致死作用更加敏感。YrbB 作用于喹诺酮类药物致细胞死亡的两种致死途径。羟自由基积累是萘啶酸介导杀伤所必需的；然而，在没有功能正常的 YrbB 的情况下，萘啶酸可以通过一种不依赖于羟自由基作用的额外机制杀伤细胞。大肠杆菌染色体毒素-抗毒素系统 ChpB 而非 SOS 系统被发现参与了羟自由基非依赖性致死机制。此外，蛋白酶 ClpP 和 Lon 也参与了 YrbB 的作用。除了喹诺酮类药物外，YrbB 还在细胞对其他应激原（如丝裂霉素 C、紫外线和过氧化氢）的反应中发挥保护作用。
YrbB 通过一种不依赖羟自由基和毒素-抗毒素依赖的机制在喹诺酮类药物的致死作用中发挥保护作用，使其成为抗菌增强的潜在靶点。
