Genome-wide analysis of the regulatory function mediated by the small regulatory psm-mec RNA of methicillin-resistant Staphylococcus aureus

Int J Med Microbiol. 2014 Jul;304(5-6):637-44. doi: 10.1016/j.ijmm.2014.04.008. Epub 2014 Apr 28.

Abstract

Several methicillin resistance (SCCmec) clusters characteristic of hospital-associated methicillin-resistant Staphylococcus aureus (MRSA) strains harbor the psm-mec locus. In addition to encoding the cytolysin, phenol-soluble modulin (PSM)-mec, this locus has been attributed gene regulatory functions. Here we employed genome-wide transcriptional profiling to define the regulatory function of the psm-mec locus. The immune evasion factor protein A emerged as the primary conserved and strongly regulated target of psm-mec, an effect we show is mediated by the psm-mec RNA. Furthermore, the psm-mec locus exerted regulatory effects that were more moderate in extent. For example, expression of PSM-mec limited expression of mecA, thereby decreasing methicillin resistance. Our study shows that the psm-mec locus has a rare dual regulatory RNA and encoded cytolysin function. Furthermore, our findings reveal a specific mechanism underscoring the recently emerging concept that S. aureus strains balance pronounced virulence and high expression of antibiotic resistance.

Keywords: Antibiotic resistance; MRSA; Staphylococcus aureus; Virulence.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Bacterial Proteins / biosynthesis
  • Bacterial Toxins / biosynthesis
  • Gene Expression Profiling
  • Gene Expression Regulation, Bacterial*
  • Humans
  • Methicillin-Resistant Staphylococcus aureus / genetics*
  • Methicillin-Resistant Staphylococcus aureus / isolation & purification
  • Penicillin-Binding Proteins
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism*
  • Staphylococcal Infections / microbiology
  • Staphylococcal Protein A / biosynthesis

Substances

  • Bacterial Proteins
  • Bacterial Toxins
  • Penicillin-Binding Proteins
  • RNA, Small Interfering
  • Staphylococcal Protein A
  • mecA protein, Staphylococcus aureus
  • staphylococcal delta toxin