Small RNA OxyS induces resistance to aminoglycosides during oxidative stress by controlling Fe-S cluster biogenesis in Escherichia coli

• 成果类型: Article
• 署名作者: Baussier, Corentin; Oriol, Charlotte; Durand, Sylvain; Py, Beatrice; Mandin, Pierre
• 署名单位: Aix-Marseille Universite; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Universite Paris Cite; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB)
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-12530
• DOI: 10.1073/pnas.2317858121
• 发表日期: 2024-11-12
• 关键词: hydrogen-peroxide; suf operon; iron starvation; assembly system; dna-damage; iscr; expression; proteins; metabolism; induction

摘要

Fe-S clusters are essential cofactors involved in many reactions across all domains of life. Their biogenesis in Escherichia coli and other enterobacteria involves two machineries: Isc and Suf. Under conditions where cells operate with the Suf system, such as during oxidative stress or iron limitation, the entry of aminoglycosides is reduced, leading to resistance to these antibiotics. The transition between Isc and Suf machineries is controlled by the transcriptional regulator IscR. Here, we found that two small regulatory RNAs (sRNAs), FnrS and OxyS, control iscR expression by base pairing to the 5 '-UTR of the iscR mRNA. These sRNAs act in opposite ways and in opposite conditions: FnrS, expressed in anaerobiosis, represses the expression of iscR while OxyS, expressed during oxidative stress, activates it. Using an E. coli strain experiencing protracted oxidative stress, we further demonstrate that iscR expression is rapidly and significantly enhanced in the presence of OxyS. Consequently, we further show that OxyS induces resistance to aminoglycosides during oxidative stress through regulation of Fe-S cluster biogenesis, revealing a major role for this sRNA.