PSM-Mec-A Virulence Determinant that Connects Transcriptional Regulation, Virulence, and Antibiotic Resistance in Staphylococci.

Li Qin,Michael Otto,Gordon Y C Cheung,Joshua W Mccausland

doi:10.3389/fmicb.2016.01293

Abstract

PSM-mec is a secreted virulence factor that belongs to the phenol-soluble modulin (PSM) family of amphipathic, alpha-helical peptide toxins produced by Staphylococcus species. All known PSMs are core genome-encoded with the exception of PSM-mec, whose gene is found in specific sub-types of SCCmec methicillin resistance mobile genetic elements present in methicillin-resistant Staphylococcus aureus and coagulase-negative staphylococci. In addition to the cytolytic translational product, PSM-mec, the psm-mec locus encodes a regulatory RNA. In S. aureus, the psm-mec locus influences cytolytic capacity, methicillin resistance, biofilm formation, cell spreading, and the expression of other virulence factors, such as other PSMs, which results in a significant impact on immune evasion and disease. However, these effects are highly strain-dependent, which is possibly due to differences in PSM-mec peptide vs. psm-mec RNA-controlled effects. Here, we summarize the functional properties of PSM-mec and the psm-mec RNA molecule and their roles in staphylococcal pathogenesis and physiology.

Highlights

Staphylococcus aureus is a serious human pathogen responsible for a multitude of human diseases, which range from acute skin and soft tissue infections to more severe illnesses such as catheter-associated bacteremia, necrotizing pneumonia, and osteomyelitis
PSM-mec belongs to the phenol-soluble modulin (PSM) family of amphipathic, alpha-helical peptide toxins produced by Staphylococcus species (Wang et al, 2007, 2011; Diep and Otto, 2008; Otto, 2014; Cheung et al, 2014a), which collectively play an important role as virulence determinants in many facets of S. aureus and S. epidermidis pathogenesis (Wang et al, 2011; Periasamy et al, 2012; Cassat et al, 2013; Cheung et al, 2014a)
We recently reported that the expression of the PSM-mec peptide impacted oxacillin resistance in S. aureus (Cheung et al, 2014b), suggesting that a delicate balance may exist between virulence gene expression and methicillin resistance in methicillin-resistant S. aureus (MRSA) strains carrying the psm-mec locus

Summary

INTRODUCTION

Staphylococcus aureus is a serious human pathogen responsible for a multitude of human diseases, which range from acute skin and soft tissue infections to more severe illnesses such as catheter-associated bacteremia, necrotizing pneumonia, and osteomyelitis. The authors reported that an open reading frame (ORF) transcribed in the opposite direction of the psm-mec gene, coined “fudoh,” encoded a protein that controlled colony spreading (Kaito et al, 2008) It was later discovered from experiments using S. aureus isogenic fudoh point-deletion mutants that the phenotypic differences were influenced by an srRNA (Kaito et al, 2011), which contains the psm-mec gene (Kaito et al, 2011, 2013), in a way similar to the genetic layout of δ-toxin, whose gene is found within the regulatory RNA of the agr system, RNAIII (Novick, 2003). In most psm-mec-positive S. aureus strains, the regulatory effect of the psm-mec srRNA on the expression of other biofilm-dispersing

Virulence determinant

Findings

CONCLUSION