The multicopy sRNA LhrC controls expression of the oligopeptide-binding protein OppA in <i>Listeria monocytogenes</i>

<i>Listeria monocytogenes</i> is the causative agent of the foodborne disease listeriosis. During infection, <i>L. monocytogenes</i> produces an array of non-coding RNAs, including the multicopy sRNA LhrC. These five, nearly identical sRNAs are highly induced in response to cell envelope stress and target the virulence adhesin <i>lapB</i> at the post-transcriptional level. Here, we demonstrate that LhrC controls expression of additional genes encoding cell envelope-associated proteins with virulence function. Using transcriptomics and proteomics, we identified a set of genes affected by LhrC in response to cell envelope stress. Three targets were significantly down-regulated by LhrC at both the RNA and protein level: <i>lmo2349, tcsA</i> and <i>oppA</i>. All three genes encode membrane-associated proteins: A putative substrate binding protein of an amino acid ABC transporter (Lmo2349); the CD4+ T cell-stimulating antigen TcsA, and the oligopeptide binding protein OppA, of which the latter 2 are required for full virulence of <i>L. monocytogenes</i>. For OppA, we show that LhrC acts by direct base paring to the ribosome binding site of the <i>oppA</i> mRNA, leading to an impediment of its translation and a decreased mRNA level. The sRNA-mRNA interaction depends on 2 of 3 CU-rich regions in LhrC allowing binding of 2 <i>oppA</i> mRNAs to a single LhrC molecule. Finally, we found that LhrC contributes to infection in macrophage-like cells. These findings demonstrate a central role for LhrC in controlling the level of OppA and other virulence-associated cell envelope proteins in response to cell envelope stress.