A small RNA controls a protein regulator involved in antibiotic resistance in Staphylococcus aureus

Abstract

The emergence of Staphylococcus aureus strains that are resistant to glycopeptides has led to alarming scenarios where serious staphylococcal infections cannot be treated. The bacterium expresses many small regulatory RNAs (sRNAs) that have unknown biological functions for the most part. Here we show that an S. aureus sRNA, SprX (alias RsaOR), shapes bacterial resistance to glycopeptides, the invaluable treatments for Methicillin-resistant staphylococcal infections. Modifying SprX expression levels influences Vancomycin and Teicoplanin glycopeptide resistance. Comparative proteomic studies have identified that SprX specifically downregulates stage V sporulation protein G, SpoVG. SpoVG is produced from the yabJ-spoVG operon and contributes to S. aureus glycopeptide resistance. SprX negatively regulates SpoVG expression by direct antisense pairings at the internal translation initiation signals of the second operon gene, without modifying bicistronic mRNA expression levels or affecting YabJ translation. The SprX and yabJ-spoVG mRNA domains involved in the interaction have been identified, highlighting the importance of a CU-rich loop of SprX in the control of SpoVG expression. We have shown that SpoVG might not be the unique SprX target involved in the glycopeptide resistance and demonstrated that the regulation of glycopeptide sensitivity involves the CU-rich domain of SprX. Here we report the case of a sRNA influencing antibiotic resistance of a major human pathogen.

SpoVG Regulates Cell Wall Metabolism and Oxacillin Resistance in Methicillin-Resistant Staphylococcus aureus Strain N315

“…Either deletion of the yabJ-spoVG operon or inhibition of spoVG expression reduces antibiotic resistance in Staphylococcus aureus (25,29). To investigate the regulatory mechanism in which SpoVG is involved in antibiotic resistance, we deleted spoVG in MRSA strain N315.…”

“…SpoVG is considered a site-specific DNA-binding protein (28). Except that spoVG is under the control of B , a small RNA SprX negatively regulates spoVG expression by direct antisense pairings at the internal translation initiation signals of spoVG, without affecting YabJ translation (29). SpoVG is one of the target genes under the control of SprX, which is involved in glycopeptide resistance.…”

The Streptococcus suis transcriptional landscape reveals adaptation mechanisms in pig blood and cerebrospinal fluid

“…Staphylococcus aureus sRNA RNAIII uses C-rich sequences in their apical loops base-pairing with RBS of target coa, spa, SA1000, and SA2353 mRNAs, resulting in preventing ribosome binding and translation initiation (Huntzinger et al 2005;Boisset et al 2007;Chevalier et al 2010;Vanderpool et al 2011). S. aureus sRNA SprX inhibits SpoVG expression through the direct interaction between a C-rich loop of SprX and RBS of target mRNA (Eyraud et al 2014). The conservation of the C-rich loop of rss24 within the Streptococcus species suggests a common function.…”

Isobaric Tags for Relative and Absolute Quantitation Proteomics Analysis of Gene Regulation by SprC in Staphylococcus Aureus

“…Small pathogenicity island RNAs of S. aureus are expressed from genomic pathogenicity islands that present virulence and antimicrobial resistance [9]. At present, at least eight small pathogenicity island RNAs (SprA-G and X) are found [9,10], and some of them have been investigated widely. SprA1 AS occludes translation initiation signals through base pairing to repress the translation of the SprA1-encoded cytolytic peptide [11].…”

“…SprD was identified as critical to the expression reduction of the Sbi immune-evasion molecule and the virulence increase of S. aureus [12]. SprX (alias RsaOR) was reported to possess a major role in glycopeptides resistance and virulence gene expression [6,10]. SprC negatively modulates the expression of the staphylococcal autolysin, reduces S. aureus phagocytosis by human leucocyte and decreases the virulence of bacteria, however, it is adverse for S. aureus resistance to oxidative stress [13].…”