Evolutionary Dynamics of Pandemic Methicillin-Sensitive Staphylococcus aureus ST398 and Its International Spread via Routes of Human Migration

Abstract

Methicillin-susceptible Staphylococcus aureus (MSSA) accounts for the majority of S. aureus infections globally, and yet surprisingly little is known about its clonal evolution. We applied comparative whole-genome sequencing (WGS) analyses to epidemiologically and geographically diverse ST398-MSSA, a pandemic lineage affecting both humans and livestock. Bayesian phylogenetic analysis predicted divergence of human-associated ST398-MSSA ~40 years ago. Isolates from Midwestern pigs and veterinarians differed substantially from those in New York City (NYC). Pig ST398 strains contained a large region of recombination representing imports from multiple sequence types (STs). Phylogeographic analyses supported the spread of ST398-MSSA along local cultural and migratory links between parts of the Caribbean, North America, and France, respectively. Applying pairwise single-nucleotide polymorphism (SNP) distances as a measure of genetic relatedness between isolates, we observed that ST398 not only clustered in households but also frequently extended across local social networks. Isolates collected from environmental surfaces reflected the full diversity of colonizing individuals, highlighting their potentially critical role as reservoirs for transmission and diversification. Strikingly, we observed high within-host SNP variability compared to our previous studies on the dominant methicillin-resistant Staphylococcus aureus (MRSA) clone USA300. Our data indicate that the dynamics of colonization, persistence, and transmission differ substantially between USA300-MRSA and ST398-MSSA. Taken together, our study reveals local and international routes of transmission for a major MSSA clone, indicating key impacts of recombination and mutation on genetic diversification and highlighting important ecological differences from epidemic USA300. Our study demonstrates extensive local and international routes of transmission for a major MSSA clone despite the lack of substantial antibiotic resistance.

The Genomic Context for the Evolution and Transmission of Community-Associated Staphylococcus aureus ST59 Through the Food Chain

“…The substitution rate in the core genome of the ST59 lineage was estimated to be 1.31 × 10 −6 substitutions per site per year [95% highest posterior density (HPD) interval = 9.89 × 10 −7 to 1.62 × 10 −6 ], corresponding to 2.80 SNPs per year (95% HPD = 2.12-3.46). This substitution rate agreed with previously published data for other S. aureus lineages and revealed a relative conservation of the mutation rate across S. aureus lineages (McAdam et al, 2012;Uhlemann et al, 2014Uhlemann et al, , 2017Moradigaravand et al, 2017).…”

Epidemiology of Staphylococcus aureus in neonates on admission to a Chinese neonatal intensive care unit

“…ST59-SCCmecIVa was the most common MRSA clone, consistent with previous studies of epidemic MRSA clones across Asia [31] and of community-associated MRSA identified in Chinese children's hospitals [32]. In this study, several MSSA (n = 10) and MRSA (n = 2) isolates belonged to ST398, which was originally reported to colonize livestock and their human handlers [33], but has recently been associated with colonization and infection in distinct human populations in Europe, the Caribbean, and the northeastern United States [34][35][36]. In China, ST398, is thought to account for as many as 20% of SSTIs caused by S. aureus [37].…”

Molecular characteristics and virulence gene profiles of Staphylococcus aureus isolates in Hainan, China

“…ST45, a common type of S. aureus isolate in Hainan, was found to have an eta prevalence of 95.7% in our results. Meanwhile, ST398, a clone with a low prevalence of pvl in previous studies [37,40], had a frequency of 81.3% in this study.…”

“…MSSA is a frequent source of S. aureus infections between individuals in households. This contrasts with the limited transmissibility of livestock-associated ST398 MRSA strains between humans [40].…”