The Arginine Catabolic Mobile Element and Staphylococcal Chromosomal CassettemecLinkage: Convergence of Virulence and Resistance in the USA300 Clone of Methicillin‐ResistantStaphylococcus aureus

Abstract

The epidemic character of community-associated methicillin-resistant Staphylococcus aureus, especially the geographically widespread clone USA300, is poorly understood. USA300 isolates carry a type IV staphylococcal chromosomal cassette mec (SCCmec) element conferring beta-lactam antibiotic class resistance and a putative pathogenicity island, arginine catabolic mobile element (ACME). Physical linkage between SCCmec and ACME suggests that selection for antibiotic resistance and for pathogenicity may be interconnected. We constructed isogenic mutants containing deletions of SCCmec and ACME in a USA300 clinical isolate to determine the role played by these elements in a rabbit model of bacteremia. We found that deletion of type IV SCCmec did not affect competitive fitness, whereas deletion of ACME significantly attenuated the pathogenicity or fitness of USA300. These data are consistent with a model in which ACME enhances growth and survival of USA300, allowing for genetic "hitchhiking" of SCCmec. SCCmec in turn protects against exposure to beta-lactams.

The role of virulence determinants in community-associated MRSA pathogenesis

“…Precise deletion of ACME in a USA300 clinical isolate resulted in attenuated pathogenicity or fitness when compared to the parental strain in the rabbit co-infection model, thereby providing evidence that ACME contributes to pathogenesis [34]. Two gene clusters identified in ACME, arc and opp-3, could confer the phenotypes of interest.…”

“…When comparing isogenic strains with different allotypes of the SCCmec element, type I SCCmec but not type IV SCCmec was found to impose a fitness cost to the bacterial host in terms of decreased in vitro growth rate and cell yield per mole of ATP consumed [63]. A highly discriminating rabbit co-infection model was used to further demonstrate that a USA300 clinical strain and its isogenic mutant with precise deletion of the type IV SCCmec exhibited no difference in infectivity of vital rabbit organs [34]. Taken together, these data strongly indicate that type IV SCCmec does not engender a biological fitness cost.…”

“…Type I ACME has been postulated to contribute to growth and survival of USA300 within the host, and promote colonization of the human skin [26]. ACME is integrated downstream of type IV SCCmec (Figure 2), utilizing the same cassette chromosome recombinases A and B (ccrAB) contained with SCCmec for mobilization and transfer [15][16][17][18][19][20][21][22][23][24]34]. Type I ACME is a distinctive genetic feature of the USA300 pandemic clone [26,34,35], although ACME-like elements have been detected in sporadic MRSA [32][33][34].…”

“…Using both co-infection and single-strain infection designs in 117 outbred rabbits, no difference in lung, spleen or kidney infectivity were detected using the same MW2 and LAC isogenic strain pairs [52]. As the same mouse and rabbit models have been used successfully to demonstrate the role of other CA-MRSA virulence factors [53,54], the null effect of PVL in these models strongly indicates that this toxin is not a major virulence factor of MW2 and USA300 strains.…”

“…Type IV SCCmec is physically linked to type I ACME in the pandemic clone USA300 (Figure 2), suggesting that selection for antibiotic resistance and pathogenicity may be interconnected [34]. Precise deletion of ACME in a USA300 clinical isolate resulted in attenuated pathogenicity or fitness when compared to the parental strain in the rabbit co-infection model, thereby providing evidence that ACME contributes to pathogenesis [34].…”