Tackling antibiotic resistance in ESKAPE pathogens through the lens of bacterial small RNAs

The worldwide emergence and spread of antimicrobial-resistant pathogens pose a significant risk to public health. The ESKAPE group of pathogens-specifically Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species has gained notoriety due to its multidrug-resistance and causing hospital-acquired infections. These pathogens are linked to higher rates of morbidity and mortality, as well as substantial economic burden. Bacterial small regulatory RNAs (sRNAs) represent a distinct class of RNA molecules and serve key functions in controlling diverse cellular processes in prokaryotic organisms. Accumulating evidence indicates that sRNAs contribute to antibiotic resistance through modulating the expression of resistance determinants, such as the drug target, the expression of porin and efflux pump, and biofilm formation. However, the complex sRNAs-mediated regulatory networks in ESKAPE pathogens remain incompletely characterized. This review focuses on the sRNA-mediated antibiotic resistance mechanisms in ESKAPE pathogens, the epidemiology and antibiotic resistance mechanisms, the regulatory role of sRNAs in antibiotic resistance genes, and their clinical implications, current challenges, and future research directions. By integrating findings from numerous studies, we offer a thorough comprehension of the intricate interactions between sRNAs and antibiotic resistance in ESKAPE pathogens-knowledge that is essential for formulating effective strategies to tackle infections associated with these pathogens.