Tolerance to antibiotics and persistence are associated with antibiotic treatment failures, chronic-relapsing infections, and emerging antibiotic resistance in various bacteria, including Staphylococcus aureus. Mechanisms of persistence are largely unknown, yet have been linked to physiology under low-ATP conditions and the metabolic-inactive state. EttA is an ATP-binding cassette protein, linked in Eschrechia coli to ribosomal hibernation and fitness in stationary growth phase, yet its role in S. aureus physiology is unknown. Using whole genome sequencing (WGS) of serial clinical isolates, we identified an EttA-negative S. aureus mutant (ettAstop), and its isogenic wild-type counterpart. We used these two isogenic clones to investigate the role of ettA in S. aureus physiology in starvation and antibiotic stress, and test its role in persistence and antibiotic tolerance. ettAstop and its WT counterpart were similar in their antibiotic resistance profiles to multiple antibiotics. Population dynamics of ettAstop and the WT were similar in low-nutrient setting, with similar recovery from stationary growth phase or starvation. Supra-bacteriocidal concentration of cefazolin had the same killing effect on ettAstop and WT populations, with no difference in persister formation. Lack of ettA does not affect S. aureus antibiotic resistance, beta-lactam tolerance, resilience to starvation or fitness following starvation. We conclude the role of ettA in S. aureus physiology is limited or redundant with another, unidentified gene. WGS of serial clinical isolates may enable investigation of other single genes involved in S. aureus virulence, and specifically persister cell formation.

中文翻译：

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EttA 可能对金黄色葡萄球菌的持久性、适应性或对抗生素的耐药性不是必需的。

对抗生素的耐受性和持久性与抗生素治疗失败、慢性复发性感染以及各种细菌（包括金黄色葡萄球菌）的抗生素耐药性有关。持久性的机制在很大程度上是未知的，但与低 ATP 条件下的生理学和代谢不活跃状态有关。EttA 是一种 ATP 结合盒蛋白，在大肠杆菌中与固定生长期的核糖体冬眠和适应性相关，但其在金黄色葡萄球菌生理学中的作用尚不清楚。使用系列临床分离株的全基因组测序 (WGS)，我们确定了 EttA 阴性金黄色葡萄球菌突变体 (ettAstop) 及其同基因野生型对应物。我们使用这两个同基因克隆来研究 ettA 在饥饿和抗生素应激中金黄色葡萄球菌生理学中的作用，并测试其在持久性和抗生素耐受性方面的作用。ettAstop 及其 WT 对应物的抗生素耐药性与多种抗生素相似。ettAstop 和 WT 的种群动态在低营养环境中相似，从稳定生长期或饥饿中恢复相似。头孢唑啉的超杀菌浓度对 ettAstop 和 WT 群体具有相同的杀灭作用，而持久性形成没有差异。缺乏 ettA 不会影响金黄色葡萄球菌的抗生素抗性、β-内酰胺耐受性、饥饿恢复能力或饥饿后的健康。我们得出的结论是 ettA 在金黄色葡萄球菌生理学中的作用与另一个未识别的基因有限或多余。系列临床分离株的 WGS 可能有助于研究金黄色葡萄球菌毒力中涉及的其他单基因，