Transcription and Translation Products of the Cytolysin Gene psm-mec on the Mobile Genetic Element SCCmec Regulate Staphylococcus aureus Virulence

Abstract

The F region downstream of the mecI gene in the SCCmec element in hospital-associated methicillin-resistant Staphylococcus aureus (HA-MRSA) contains two bidirectionally overlapping open reading frames (ORFs), the fudoh ORF and the psm-mec ORF. The psm-mec ORF encodes a cytolysin, phenol-soluble modulin (PSM)-mec. Transformation of the F region into the Newman strain, which is a methicillin-sensitive S. aureus (MSSA) strain, or into the MW2 (USA400) and FRP3757 (USA300) strains, which are community-acquired MRSA (CA-MRSA) strains that lack the F region, attenuated their virulence in a mouse systemic infection model. Introducing the F region to these strains suppressed colony-spreading activity and PSMα production, and promoted biofilm formation. By producing mutations into the psm-mec ORF, we revealed that (i) both the transcription and translation products of the psm-mec ORF suppressed colony-spreading activity and promoted biofilm formation; and (ii) the transcription product of the psm-mec ORF, but not its translation product, decreased PSMα production. These findings suggest that both the psm-mec transcript, acting as a regulatory RNA, and the PSM-mec protein encoded by the gene on the mobile genetic element SCCmec regulate the virulence of Staphylococcus aureus.

Distinct Roles of Phenol-Soluble Modulins in Spreading of Staphylococcus aureus on Wet Surfaces

“…We observed no role for the PSM-mec neither in the promotion nor the inhibition of spreading. The latter observations are intriguing, because it has been reported that the PSM-mec and/or the PSM-mec mRNA can inhibit colony spreading (47). Since the synthetic PSM-mec peptides gave no phenotype, whereas other synthetic PSM peptides were active, it seems most likely that the previously reported effects do not relate to a translated product but rather to a regulatory effect of the psm-mec gene.…”

“…3). Based on genetic studies, it was previously proposed that PSM-mec might inhibit colony spreading (47). We therefore tested the synthetic PSM-mec peptide for possible inhibitory effects, but unfortunately, no such effects were detectable in our experimental setting (Fig.…”

MRSA and MSSA: The Mechanism of Methicillin Resistance and the Influence of Methicillin Resistance on Biofilm Phenotype of Staphylococcus aureus

“…As a result of reduced expression of PSMα toxin, virulence of S. aureus is reduced by PSMmec (Figure 3) [45,46]. Bioilm formation (adherence to surfaces and intercellular aggregations) of MSSA and MRSA strains is contributed by PIA in ica-dependent manner and surface proteins in ica-independent manner, respectively [4,14].…”

Inhibition of Colony-spreading Activity of Staphylococcus aureus by Secretion of δ-Hemolysin

“…In addition to ␦-hemolysin, other PSMs include PSM␣1, -␣2, -␣3, -␣4, -␤1, and -␤2 (34). We and other researchers demonstrated that S. aureus colony-spreading activity requires the psm␣ operon, which encodes PSM␣1, -␣2, -␣3, and -␣4, and whose expression depends on the agr locus (11,35). We and others also reported that the agr locus is required for S. aureus colony spreading (31,35).…”

“…The correlation between high colony-spreading activity and high virulence of S. aureus strains suggests that colony spreading has a role in the infectious processes of S. aureus (10). The difference in colony-spreading activity and virulence between HA-MRSA and CA-MRSA is attributed to the virulence regulatory RNA harbored specifically in the SCCmec region of the HA-MRSA strain (11). Determining the regulatory mechanism of S. aureus colony spreading is important for understanding the virulence properties of S. aureus.…”