The regulatory RNA Ern0160 is involved in pathogenicity of Enterococcus faecium

In this study, we aimed to further characterize Ern0160 functions and identify its targets. In silico prediction screen highlighted putative mRNA candidates. For two of them, homologous genes encoding for LysM-containing domain proteins (EFAU004_01059 and EFAU004_01150), we validated a direct and specific interaction to Ern0160. In addition, we found that Ern0160 overexpression was responsible for the repression of the target genes, emphasizing the mode of action of this sRNA. As a recent study provided the role of these genes in the virulence of E. faecium Aus0004 in a mouse model of systemic and urinary tract infections, we proposed that Ern0160 could be part of the regulatory network involved during colonization/infection by attenuating virulence. Furthermore, in vitro tests of antibiotic susceptibility profiles to vancomycin, teicoplanin, daptomycin, ciprofloxacin, and levofloxacin showed that a strain expressing Ern0160 presented lower MICs of fluoroquinolones compared to a ern0160-deleted strains. Very interestingly, we found that a gene implicated in fluoroquinolone resistance in E. faecium, Efmqnr was downregulated when Ern0160 was over-expressed, indicating a link between this sRNA and antibiotic resistance. For the first time, this study investigated throughout the identification of its cellular targets the regulation that could lead to virulence and fluoroquinolone resistance in E. faecium. Transcriptome analysis by RNA-seq to compare the levels of all transcripts in ern0160-deleted E. faecium Aus0004 mutant versus wild-type strain and in trans-complemented srn0160-deleted E. faecium Aus0004 mutant versus srn0160-deleted E. faecium Aus0004 mutant with empty plasmid