Institute of Ecology and Genetics of Microorganisms, Perm Federal Research Center, Russian Academy of Sciences, Goleva 13, 614081, Perm, Russia.
Arch Microbiol. 2024 Nov 4;206(12):456. doi: 10.1007/s00203-024-04185-z.
Endogenous HS has been proposed to be a universal defense mechanism against different antibiotics. Here, we studied the role of HS transiently generated during ciprofloxacin (CF) treatment in M9 minimal medium with sulfate or produced by E. coli when fed with cystine. The cysM and mstA mutants did not produce HS, while gshA generated more HS in response to ciprofloxacin in cystine-free media. All mutants showed a reduced ability to maintain cysteine homeostasis under these conditions. We found no relationship between HS generation, cysteine concentration and sensitivity to ciprofloxacin. Excess cysteine, which occurred during E. coli growth in cystine-fed media, triggered continuous HS production, accelerated glutathione synthesis and cysteine export. This was accompanied by a twofold increase in ciprofloxacin tolerance in all strains except gshA, whose sensitivity increased 5-8-fold at high CF doses, indicating the importance of GSH in restoring the intracellular redox situation during growth in cystine-fed media.
内源性 HS 被认为是对抗不同抗生素的通用防御机制。在这里，我们研究了在含有硫酸盐的 M9 基础培养基中或在喂食胱氨酸时大肠杆菌产生的、环丙沙星（CF）治疗过程中短暂产生的 HS 的作用。cysM 和 mstA 突变体不产生 HS，而 gshA 在无胱氨酸的培养基中对环丙沙星的反应生成更多的 HS。所有突变体在这些条件下维持半胱氨酸稳态的能力都降低了。我们没有发现 HS 生成、半胱氨酸浓度和对环丙沙星敏感性之间的关系。在胱氨酸喂养的培养基中大肠杆菌生长过程中产生的过量半胱氨酸会触发持续的 HS 生成，加速谷胱甘肽合成和半胱氨酸输出。除 gshA 外，所有菌株的环丙沙星耐受性都增加了两倍，而 gshA 在高 CF 剂量下的敏感性增加了 5-8 倍，这表明 GSH 在恢复胱氨酸喂养培养基中生长时细胞内氧化还原状态的重要性。
