Abstract
USA300 is a predominant community-associated methicillin-resistant Staphylococcus aureus strain which carries an arginine catabolic mobile element (ACME). ACME contains potential virulence factors including an arginine deiminase (arc) pathway and an oligopeptide permease (opp-3) system, which are proposed to play a role in bacterial virulence and transmission. However, the role of ACME in evolution and pathogenicity of USA300 remains to be elucidated. ACME and arcA deletion mutants were created by allelic replacement from a USA300 clinical isolate. By comparing wild type and isogenic ACME deletion USA300 strains, ACME was shown not to contribute to bacterial survival on plastic surfaces, and mouse skin surfaces. ACME did not contribute to bacterial virulence in cell invasion and cytotoxicity assays, invertebrate killing assays and a mouse skin infection model. Wild-type ACME negative USA300 clinical isolates showed similar associations with invasive anatomic sites as ACME positive isolates. Our experiments also demonstrated that ACME can spontaneously excise from the bacterial chromosome to generate an ACME deletion strain at a low frequency. Our results do not support that the ACME element alone is a significant factor in the transmission and virulence of USA300 strain, and ACME may have been coincidently incorporated into the genome of USA300.
Highlights
Staphylococcus aureus is a Gram-positive, coagulase-positive coccus of approximately 1 μm in diameter forming grape-like clusters
The genome sequence of the Community-associated methicillin-resistant S. aureus (CA-MRSA) predominant strain USA300 has revealed the presence of a unique genomic island, arginine catabolic mobile element (ACME), in USA300, and ACME has been hypothesized to contribute to the enhanced virulence and transmission of USA300 [4,30]
In a rabbit bacteremia model, Diep et al demonstrated that wild type (WT) and an SCCmec deletion mutant strain (SCCmec−) have the same fitness but the WT strain shows better fitness than the ACME-SCCmec deletion mutant strain (ACME-SCCmec−), indirectly suggesting that ACME contributes to bacterial fitness [10]
Summary
Staphylococcus aureus is a Gram-positive, coagulase-positive coccus of approximately 1 μm in diameter forming grape-like clusters. A key enzyme in this catabolic pathway, is a virulence factor in Streptococcus pyogenes, which inhibits proliferation of human T-cells [6] and enhances bacterial invasion and survival at low pH intracellular environment [7]. Using a rodent model of necrotizing pneumonia and skin infection, Montgomery et al demonstrated no difference in survival, bacterial burden and appearances of lesions among the wild type (WT), isogenic ACME deletion mutant strains and ACME negative (ACME−) USA300 clinical isolates, suggesting that ACME is not necessary for the virulence of USA300 in these models [11]. The role of ACME in bacterial colonization and transmission, which is another significant characteristic of USA300 strains, has not been investigated to date
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