title: A feed-forward loop between SroC and MgrR small RNAs modulates the expression of eptB and the susceptibility to polymyxin B in Salmonella Typhimurium.
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 ΔmgrR and ΔsroCΔmgrR 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.
authors: Laboratorio de Genética y Patogénesis Bacteriana, Facultad de Ciencias Biológicas, Universidad Andres Bello, Santiago, Chile.|Laboratorio de Ecofisiología Microbiana, Fundación Ciencia para la Vida, Santiago, Chile.
authors: Lillian G
authors: LG
authors: Acuña
authors: Laboratorio de Genética y Patogénesis Bacteriana, Facultad de Ciencias Biológicas, Universidad Andres Bello, Santiago, Chile.
authors: M José
authors: MJ
authors: Barros
authors: Laboratorio de Genética y Patogénesis Bacteriana, Facultad de Ciencias Biológicas, Universidad Andres Bello, Santiago, Chile.
authors: Diego
authors: D
authors: Peñaloza
authors: Center for Integrative Medicine and Innovative Sciences, Facultad de Medicina, Universidad Andres Bello, Santiago, Chile.
authors: Paula I
authors: PI
authors: Rodas
authors: Departamento de Ciencias Biológicas, Microbiota-Host Interaction and Clostridia Research Group, Facultad de Ciencias Biológicas, Universidad Andres Bello, Santiago, Chile.|Center for Bioinformatics and Integrative Biology, Facultad de Ciencias Biológicas, Universidad Andres Bello, Santiago, Chile.
authors: Daniel
authors: D
authors: Paredes-Sabja
authors: Laboratorio de Genética y Patogénesis Bacteriana, Facultad de Ciencias Biológicas, Universidad Andres Bello, Santiago, Chile.
authors: Juan A
authors: JA
authors: Fuentes
authors: Laboratorio de Genética y Patogénesis Bacteriana, Facultad de Ciencias Biológicas, Universidad Andres Bello, Santiago, Chile.
authors: Fernando
authors: F
authors: Gil
authors: Laboratorio de Genética y Patogénesis Bacteriana, Facultad de Ciencias Biológicas, Universidad Andres Bello, Santiago, Chile.
authors: Iván L
authors: IL
authors: Calderón
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics* / Q000378:metabolism; D011112:Polymyxin B / Q000494:pharmacology*; D012329:RNA, Bacterial / Q000235:genetics / Q000378:metabolism*; D022661:RNA, Untranslated / Q000235:genetics / Q000378:metabolism*; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000201:enzymology* / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D012329:RNA, Bacterial; D022661:RNA, Untranslated; D017853:Phosphotransferases (Alcohol Group Acceptor); D011112:Polymyxin B