PhoQ/P-regulated small RNA regulates sensitivity of Escherichia coli to antimicrobial peptides

• Published in: Molecular microbiology Vol. 74; no. 6; pp. 1314 - 1330
• Main Authors: Moon, Kyung, Gottesman, Susan
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01.12.2009; Blackwell Publishing Ltd
• Subjects: Anti-Bacterial Agents - pharmacology; Bacterial proteins; Bacterial Proteins - physiology; Base Sequence; Binding sites; E coli; Escherichia coli; Escherichia coli - drug effects; Escherichia coli - physiology; Escherichia coli Proteins - metabolism; Escherichia coli Proteins - physiology; Gene Deletion; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Bacterial; Host Factor 1 Protein - metabolism; Microbial Sensitivity Tests; Microbiology; Molecular Sequence Data; Oligonucleotide Array Sequence Analysis; Peptides; Polymyxin B - pharmacology; Protein Binding; Ribonucleic acid; RNA; RNA, Bacterial - biosynthesis; RNA, Bacterial - genetics; RNA, Untranslated - biosynthesis; RNA, Untranslated - genetics; Salmonella; Salmonella - genetics; Sequence Alignment
• ISSN: 0950-382X; 1365-2958; 1365-2958
• DOI: 10.1111/j.1365-2958.2009.06944.x

Non-coding small RNAs (sRNAs) play a major role in post-transcriptional regulation of gene expression. Of the 80 sRNAs that have been identified in E. coli, one-third bind to the RNA chaperone Hfq. Hfq both stabilizes these sRNAs in vivo and stimulates pairing to targets in vitro. A novel Hfq-dependent RNA, called here MgrR, was identified by its ability to bind Hfq. Expression of MgrR requires the PhoQ/PhoP two-component system; the PhoP response regulator is active under low Mg²⁺ concentrations and is an important virulence regulator in Salmonella; mgrR is also found in Salmonella species. Negatively regulated targets of MgrR identified using microarrays include eptB, involved in lipopolysaccharide (LPS) modification, and ygdQ, encoding a hypothetical protein. Cell sensitivity to the antimicrobial polymyxin B is affected by LPS modifications, and cells carrying an mgrR deletion were approximately 10 times more resistant than wild-type cells to polymyxin B. Thus, lower Mg²⁺ concentrations, sensed by PhoQ/PhoP, lead to expression of MgrR, changing LPS. sRNAs have previously been shown to regulate many outer membrane proteins. This work demonstrates that LPS, a major contributor of bacterial interactions with mammalian cells, is also subject to regulation by sRNAs.