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.

Highlights

  • Staphylococcus aureus is a pathogenic bacterium that causes various diseases in humans

  • The different virulence phenotypes of these two methicillin resistant S. aureus (MRSA) is suggested to be due to Panton-Valentine leukocidin (PVL) [9,10], which is encoded on lysogenized bacteriophages, a mobile genetic element [11], or phenol-soluble modulin a (PSMa), which is encoded in the core genome [12]

  • We focused our attention on the structural difference of the SCCmec region between hospital-associated MRSA (HA-MRSA) and community-acquired MRSA (CA-MRSA)

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Summary

Introduction

Staphylococcus aureus is a pathogenic bacterium that causes various diseases in humans. The emergence of methicillin resistant S. aureus (MRSA), vancomycin resistant S. aureus, and community acquired MRSA (CA-MRSA) is a serious clinical problem [1,2,3,4] These MRSA species are thought to have evolved by acquiring mobile genetic elements that carry antibiotic resistance genes or virulence genes [5]. We examined whether introducing the F region into CA-MRSA strains decreases colony-spreading ability Both the F region-introduced MW2 and F regionintroduced FRP3757 strains showed decreased colony-spreading ability compared with the empty vector-introduced parent strains (Fig. 2C, D). These results suggest that absence of the F region underlies the virulence of CA-MRSA strains in causing systemic diseases as well as colony spreading ability

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