Virulence strategies of the dominant USA300 lineage of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA)

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) poses a serious threat to worldwide health. Historically, MRSA clones have strictly been associated with hospital settings, and most hospital-associated MRSA (HA-MRSA) disease resulted from a limited number of virulent clones. Recently, MRSA has spread into the community causing disease in otherwise healthy people with no discernible contact with healthcare environments. These community-associated MRSA clones (CA-MRSA) are phylogenetically distinct from traditional HA-MRSA clones, and CA-MRSA strains seem to exhibit hypervirulence and more efficient host : host transmission. Consequently, CA-MRSA clones belonging to the USA300 lineage have become dominant sources of MRSA infections in North America. The rise of this successful USA300 lineage represents an important step in the evolution of emerging pathogens and a great deal of effort has been exerted to understand how these clones evolved. Here, we review much of the recent literature aimed at illuminating the source of USA300 success and broadly categorize these findings into three main categories: newly acquired virulence genes, altered expression of common virulence determinants and alterations in protein sequence that increase fitness. We argue that none of these evolutionary events alone account for the success of USA300, but rather their combination may be responsible for the rise and spread of CA-MRSA.

Figure 1. Schematic representation of the evolution of MRSA

Sequence Types (STs) belonging to established Clonal Complexes (CCs) are colored as follows: CC1, purple; CC5, green; CC8, red; CC22, orange; CC30, blue; CC45, black. ST59 has not been assigned to a CC. Roman numerals reflect acquired SCCmec type. Commonly used S. aureus strains are depicted around their relevant ST symbol.

Figure 2. Association between arc gene cluster and speG in ACME. TOP

ACME type I, found in USA300 S. aureus and also found in many S. epidermidis isolates, and ACME type II, found primarily in S. epidermidis, both harbor arc gene clusters as well as speG. ACME type III (not shown) lacks an identifiable arc gene cluster but does contain an opp-3 locus. BOTTOM: Fate of host arginine depends on competition between iNOS and Arginase-1 enzyme activities. The net production of ornithine by Arc-expressing S. aureus may skew the fate of host arginine down the polyamine synthesis pathway thereby necessitating speG.