Identification of sRNAs involved in antibiotic resistance in Salmonella.

The bacterial resistance to antimicrobial drugs has become an increasing clinical problem. Mechanisms of bacterial defense against antibiotics include mutation of the drug target, inactivation or destruction of the agent, inhibition of cell division during exposition to certain antibiotics and repression of transport systems to avoid the antimicrobial entry. Such defense pathways often rely on transcription factors of known stress regulons. In contrast, whether small noncoding RNAs (sRNAs)—an emerging class of bacterial post-transcriptional regulators--are also involved in the control of bacterial adaptability to antimicrobial agents is little understood.

Many sRNAs depend on Hfq for their base-pairing with trans-encoded target mRNAs and intracellular stability. To date, Hfq is considered as one of the major post-transcriptional regulators of the gene expression in Gram-negative bacteria. A deletion of the hfq gene causes pleiotropic phenotypes, affecting growth rate, cell morphology, tolerance of stress condition and virulence in a broad range of bacteria. Moreover, Hfq has been reported to contribute to resistance to antimicrobial peptides in meningococcus and uropathogenic E.coli, probably through helping sRNAs regulate the master regulators of bacterial stress responses, RpoS and RpoE.

We have previously shown that Hfq controls the expression of almost a fifth of all Salmonella genes. Here we have used RNA-seq of Hfq-associated RNA treated with different antibiotics to understand which sRNAs might function in regulation of the cascades that control antibiotic resistance in Salmonella enterica serovar Typhimurium SL1344, and which mRNAs are targeted by Hfq to mitigate the lethality of drugs.