Small RNA-Mediated Metabolic Reprogramming Enables Ciprofloxacin Utilization in Klebsiella sp. SG01

Abstract

Small regulatory RNAs (sRNAs) play a key role in the complex regulatory networks that bacteria use to adapt to antibiotic stress. This study clarifies how sRNAs help Klebsiella sp. SG01 metabolically adapts to ciprofloxacin (CIP). Nine potential sRNAs that target important metabolic and stress-response pathways were identified by transcriptomic profiling, including glmZ, sgrS, gcvB, and spot42, as well as an FMN riboswitch. TargetRNA3 and IntaRNA functional annotation predicted regulatory effects on TCA cycle flux, redox balance, and the transport of sugars and amino acids. Interestingly, repression of CRP and upregulation of spot42 imply that byproducts of CIP degradation resemble a glucose-rich state. This conjecture was supported by metabolomics, which verified the buildup of short-chain acids and purine intermediates. A change in regulation was also noted, with ProQ and CsrA levels rising in tandem with Hfqs downregulation. Our knowledge of microbial metabolic plasticity under xenobiotic pressure has been expanded by these findings, which collectively reveal a novel post-transcriptional mechanism that permits antibiotic assimilation and stress resilience in bacteria.