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

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Fecha
2016-11
Profesor/a Guía
Facultad/escuela
Idioma
en
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Editor
Microbiology Society
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Licencia CC
Atribution 4.0 International (CC BY 4.0)
Licencia CC
Resumen
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.
Notas
Indexación: Scopus.
ACKNOWLEDGEMENTS This work received financial support from Vicerrectoría de Investiga ción Universidad Andres Bello (UNAB DI-1327-16/R to I.L.C.) and Fondo Nacional de Desarrollo Científico y Tecnológico (FONDECYT 11110216 to I.L.C., 1130074 to F.G., 11121506 to J.A.F., 1151025 to D.P.S. and 11121262 to P.I.R.).
Palabras clave
sRNAs, RNA sponge, SroC, MgrR, Polymyxin B
Citación
Microbiology (United Kingdom). Volume 162, Issue 11, Pages 1996 - 2004. November 2016. Article number 000365
DOI
DOI: 10.1099/mic.0.000365
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