A PhoQ/P-regulated small RNA regulates sensitivity of Escherichia coli to antimicrobial peptides.
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.
Moon
Kyung
K
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
Gottesman
Susan
S
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000502:physiology*; D001483:Base Sequence; D004926:Escherichia coli / Q000187:drug effects / Q000502:physiology*; D029968:Escherichia coli Proteins / Q000378:metabolism / Q000502:physiology*; D017353:Gene Deletion; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D035001:Host Factor 1 Protein / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D011112:Polymyxin B / Q000494:pharmacology*; D011485:Protein Binding; D012329:RNA, Bacterial / Q000096:biosynthesis* / Q000235:genetics; D022661:RNA, Untranslated / Q000096:biosynthesis* / Q000235:genetics; D012475:Salmonella / Q000235:genetics; D016415:Sequence Alignment
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; C087373:Hfq protein, E coli; D035001:Host Factor 1 Protein; C465562:PhoP protein, E coli; C079792:PhoQ protein, Bacteria; D012329:RNA, Bacterial; D022661:RNA, Untranslated; D011112:Polymyxin B