A feed-forward loop between SroC and MgrR small RNAs modulates the expression of eptB and the susceptibility to polymyxin B in Salmonella Typhimurium

Lillian G. Acuña, M. José Barros, Diego Peñaloza, Paula I. Rodas, Daniel Paredes-Sabja, Juan A. Fuentes, Fernando Gil, Iván L. Calderón

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Base-pairing small RNAs (sRNAs) regulate gene expression commonly by direct interaction with cognate mRNAs. Nevertheless, recent studies have expanded this knowledge with the discovery of the RNA ‘sponges’ which are able to interact and repress the functions of classical base-pairing sRNAs. In this work, we present evidence indicating that the sponge RNA SroC from Salmonella enterica serovar Typhimurium base pairs with the MgrR sRNA, thereby antagonizing its regulatory effects on both gene expression and resistance to the antimicrobial peptide polymyxin B (PMB). By a predictive algorithm, we determined putative SroC-MgrR base-pairing regions flanking the interaction area between MgrR and its target mRNA, eptB, encoding a LPS-modifying enzyme. With a two-plasmid system and compensatory mutations, we confirmed that SroC directly interacts and down-regulates the levels of MgrR, thus relieving the MgrR-mediated repression of eptB mRNA. Since it was previously shown that an Escherichia coli strain carrying an mgrR deletion is more resistant to PMB, we assessed the significance of SroC in the susceptibility of S. Typhimurium to PMB. Whereas the sroC deletion increased the sensitivity to PMB, as compared to the wild-type, the resistance phenotypes between the DmgrR and DsroCDmgrR strains were comparable, evidencing that mgrR mutation is epistatic to the sroC mutation. Together, these results indicate that both SroC and MgrR sRNAs compose a coherent feed-forward loop controlling the eptB expression and hence the LPS modification in S. Typhimurium.

Original languageEnglish
Article number000365
Pages (from-to)1996-2004
Number of pages9
JournalMicrobiology (United Kingdom)
Volume162
Issue number11
DOIs
Publication statusPublished - Nov 2016

Keywords

  • MgrR
  • Polymyxin B
  • RNA sponge
  • SroC
  • sRNAs

ASJC Scopus subject areas

  • Microbiology

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