The golden age of antibiotics has passed, and the threat of untreatable antimicrobial resistant infections is now a reality for many individuals. Understanding how bacteria resist antimicrobial treatment and regulate gene expression in response to antibiotics is an important step towards combating resistance. In this review we focus on a ubiquitous class of bacterial gene regulators termed regulatory small RNAs (sRNAs) and how they contribute to antimicrobial resistance and tolerance. Small RNAs have notable roles in modulating the composition of the bacterial envelope, and through these functions control intrinsic antimicrobial resistance in many human pathogens. Recent technical advances that allow profiling of the ‘sRNA interactome’ have revealed a complex post-transcriptional network of sRNA interactions that can be used to identify network hubs and regulatory bottlenecks. Sequence-specific inhibition of these sRNAs with programmable RNA-targeting therapeutics may present avenues for treating antimicrobial resistant pathogens or resensitizing to our current antibiotics.

抗生素的黄金时代已经过去，不可抗药的耐药性感染的威胁现在已经成为许多人的现实。了解细菌如何抵抗抗生素治疗并响应抗生素而调节基因表达是抵抗耐药性的重要一步。在这篇综述中，我们着眼于一类普遍存在的称为调节小RNA（sRNA）的细菌基因调节剂，以及它们如何促进抗菌素耐药性和耐受性。小RNA在调节细菌包膜的组成方面起着显著作用，并通过这些功能控制许多人类病原体的固有抗药性。允许对“ sRNA相互作用基因组”进行分析的最新技术进步已揭示了一个复杂的sRNA相互作用转录后网络，可用于识别网络中心和调节瓶颈。用可编程的靶向RNA的治疗剂对这些sRNA的序列特异性抑制可能为治疗抗药性病原体或使我们目前的抗生素重新敏化提供了途径。