Department of Medicine, Division of Infectious Diseases, University at Buffalo, Buffalo, New York, USA.
Department of Biochemistry, University at Buffalo, Buffalo, New York, USA.
Antimicrob Agents Chemother. 2021 Jun 17;65(7):e0001321. doi: 10.1128/AAC.00013-21.
The SOS response to DNA damage is a conserved stress response in Gram-negative and Gram-positive bacteria. Although this pathway has been studied for years, its relevance is still not familiar to many working in the fields of clinical antibiotic resistance and stewardship. Under some conditions, the SOS response favors DNA repair and preserves the genetic integrity of the organism. On the other hand, the SOS response also includes induction of error-prone DNA polymerases, which can increase the rate of mutation, called the mutator phenotype or "hypermutation." As a result, mutations can occur in genes conferring antibiotic resistance, increasing the acquisition of resistance to antibiotics. Almost all of the work on the SOS response has been on bacteria exposed to stressors . In this study, we sought to quantitate the effects of SOS-inducing drugs , in comparison with the same drugs . We used a rabbit model of intestinal infection with enteropathogenic Escherichia coli strain E22. SOS-inducing drugs triggered the mutator phenotype response as well as . Exposure of E. coli strain E22 to ciprofloxacin or zidovudine, both of which induce the SOS response , resulted in increased antibiotic resistance to 3 antibiotics: rifampin, minocycline, and fosfomycin. Zinc was able to inhibit the SOS-induced emergence of antibiotic resistance , as previously observed . Our findings may have relevance in reducing the emergence of resistance to new antimicrobial drugs.
SOS 响应是革兰氏阴性和阳性细菌中一种保守的应激反应。尽管该途径已被研究多年，但许多从事临床抗生素耐药性和管理工作的人仍然不熟悉它。在某些条件下，SOS 反应有利于 DNA 修复并保护生物体的遗传完整性。另一方面，SOS 反应还包括诱导易错 DNA 聚合酶，这会增加突变率，称为突变表型或“超突变”。因此，抗生素耐药性相关基因可能会发生突变，从而增加对抗生素的耐药性。几乎所有关于 SOS 反应的工作都集中在暴露于应激源的细菌上。在这项研究中，我们试图定量比较诱导 SOS 的药物与相同药物的作用。我们使用了一种兔肠道感染肠致病性大肠杆菌 E22 的模型。SOS 诱导药物引发了突变表型反应以及抗生素耐药性的增加。大肠杆菌 E22 暴露于环丙沙星或齐多夫定（均诱导 SOS 反应）导致对 3 种抗生素的耐药性增加：利福平、米诺环素和磷霉素。锌能够抑制 SOS 诱导的抗生素耐药性的出现，如先前观察到的那样。我们的发现可能与减少新抗菌药物耐药性的出现有关。
