Abstract
Staphylococcus aureus USA300 represents the dominant community-associated methicillin-resistant S. aureus lineage in the USA, where it is a major cause of skin and soft tissue infections. Previous comparative genomic studies have described the population structure and evolution of USA300 based on geographically restricted isolate collections. Here, we investigated the USA300 population by sequencing genomes of a geographically distributed panel of 191 clinical S. aureus isolates belonging to clonal complex 8 (CC8), derived from the Tigecycline Evaluation and Surveillance Trial program. Isolates were collected at 12 healthcare centres across nine USA states in 2004, 2009 or 2010. Reconstruction of evolutionary relationships revealed that CC8 was dominated by USA300 isolates (154/191, 81 %), which were heterogeneous and demonstrated limited phylogeographic clustering. Analysis of the USA300 core genomes revealed an increase in median pairwise SNP distance from 62 to 98 between 2004 and 2010, with a stable pattern of above average dN/dS ratios. The phylogeny of the USA300 population indicated that early diversification events led to the formation of nested clades, which arose through cumulative acquisition of predominantly non-synonymous SNPs in various coding sequences. The accessory genome of USA300 was largely homogenous and consisted of elements previously associated with this lineage. We observed an emergence of SCCmec negative and ACME negative USA300 isolates amongst more recent samples, and an increase in the prevalence of ϕSa5 prophage. Together, the analysed S. aureus USA300 collection revealed an evolving pan-genome through increased core genome heterogeneity and temporal variation in the frequency of certain accessory elements.
Highlights
Staphylococcus aureus is a major cause of human disease worldwide
While previous studies describing the comparative genomics of USA300 focused on geographically restricted isolate collections, here we describe whole-genome sequence analysis of S. aureus clonal complex 8 (CC8) derived from 12 USA healthcare centres located across nine states
We investigated whether the chromosomally-inserted mobile genetic element (MGE) carried by USA300 diversified over time leading to temporal variation in the distribution of pairwise single nucleotide polymorphism (SNP) distances
Summary
One of the most successful lineages of this bacterial species is clonal complex 8 (CC8), from which a number of major methicillin-resistant S. aureus (MRSA) clones have emerged (Deurenberg & Stobberingh, 2008). This includes several pandemic MRSA clones associated with causing healthcare-associated (HA) infections as well as community-associated (CA) infections (Monecke et al, 2011). In addition to being responsible for a rising incidence of CA infections, USA300 has been increasingly reported in association with nasal colonisation (Freitas et al, 2010; Tenover et al, 2008) and HA infections (Gonzalez et al, 2006; Patel et al, 2007; Seybold et al, 2006). USA300 was reported to emerge alongside established HA-MRSA clones (Chua et al, 2008; Limbago et al, 2009; Pasquale et al, 2013; Tattevin et al, 2009) or to replace them (Carey et al, 2010; Liu et al, 2008)
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