Ranganathan Nisha, Johnson Rebecca, Edwards Andrew M
MRC Centre for Molecular Bacteriology and Infection, Imperial College London, Armstrong Rd, London, SW7 2AZ, UK.
Present address: Charing Cross Hospital, Fulham, Palace Road, W6 8RF, UK.
Microbiology (Reading). 2020 Nov;166(11):1088-1094. doi: 10.1099/mic.0.000983. Epub 2020 Oct 23.
is a frequent cause of invasive human infections such as bacteraemia and infective endocarditis. These infections frequently relapse or become chronic, suggesting that the pathogen has mechanisms to tolerate the twin threats of therapeutic antibiotics and host immunity. The general stress response of is regulated by the alternative sigma factor B (σB) and provides protection from multiple stresses including oxidative, acidic and heat. σB also contributes to virulence, intracellular persistence and chronic infection. However, the protective effect of σB on bacterial survival during exposure to antibiotics or host immune defences is poorly characterized. We found that σB promotes the survival of exposed to the antibiotics gentamicin, ciprofloxacin, vancomycin and daptomycin, but not oxacillin or clindamycin. We also found that σB promoted staphylococcal survival in whole human blood, most likely via its contribution to oxidative stress resistance. Therefore, we conclude that the general stress response of may contribute to the development of chronic infection by conferring tolerance to both antibiotics and host immune defences.
是侵袭性人类感染（如菌血症和感染性心内膜炎）的常见病因。这些感染经常复发或变为慢性感染，这表明该病原体具有耐受治疗性抗生素和宿主免疫双重威胁的机制。的一般应激反应由替代西格玛因子B（σB）调节，并提供针对多种应激（包括氧化应激、酸性应激和热应激）的保护。σB还对毒力、细胞内存活和慢性感染有贡献。然而，σB在暴露于抗生素或宿主免疫防御期间对细菌存活的保护作用尚未得到充分表征。我们发现，σB促进了暴露于抗生素庆大霉素、环丙沙星、万古霉素和达托霉素（但不包括苯唑西林或克林霉素）的存活。我们还发现，σB促进了葡萄球菌在全人血中的存活，最有可能是通过其对氧化应激抗性的贡献。因此，我们得出结论，的一般应激反应可能通过赋予对抗生素和宿主免疫防御的耐受性而有助于慢性感染的发展。
