Genomic Analysis of emm59 Group A Streptococcus Invasive Strains, United States

Nahuel Fittipaldi, Randall J. Olsen, Stephen B. Beres, Chris Van Beneden, and James M. Musser

Author affiliations: The Methodist Hospital Research Institute, Houston, Texas, USA (N. Fittipaldi, R.J. Olsen, S.B. Beres, J.M. Musser); Centers for Disease Control and Prevention, Atlanta, Georgia, USA (C. Van Beneden)

Abstract

Genomic analysis of type emm59 group A Streptococcus invasive strains isolated in the United States discovered higher than anticipated genetic heterogeneity among strains and identified a heretofore unrecognized monoclonal cluster of invasive infections in the San Francisco Bay area. Heightened monitoring for a potential shift in the epidemic behavior of emm59 group A Streptococcus is warranted.

Group A Streptococcus (GAS) causes human diseases ranging in severity from uncomplicated pharyngitis to life-threatening necrotizing fasciitis (1). GAS strains have traditionally been classified based on a serologic reaction against the M protein, a polymorphic cell surface adhesin and anti-phagocytic factor; GAS strains are currently typed by sequencing the 5′ hypervariable region of the emm gene, encoding M protein (2–4). Studies of large numbers of GAS isolates causing invasive infections and pharyngitis worldwide have shown that type emm59 GAS strains rarely cause disease (5,6). However, an increase in the frequency and severity of invasive infections caused by type emm59 strains (>500 cases since 2006) has been reported recently in Canada (7). One of the most striking features of the emm59 epidemic in Canada was its rapid spread; invasive emm59 disease was reported in most Canadian provinces and territories in a matter of only a few years (7). By using whole-genome sequencing and animal models of invasive disease, we recently discovered that virtually all type emm59 GAS invasive cases in Canada were caused by a single, recently emerged, hypervirulent emm59 clone (8).
Whole-genome sequence analysis also revealed distinct spatiotemporal patterns of subclone diversification of the epidemic clone in Canada (8). Furthermore, we discovered that several geographically clustered cases of type emm59 GAS invasive infections in south-central Montana in 2010 were caused by a distinct subclone of the emm59 epidemic clone that disseminated from Canada (8). This finding led us to evaluate the hypothesis that the epidemic emm59 clone disseminated further and caused invasive infections in other regions of the United States.

The Study

In this study, we sequenced the genomes of all available invasive emm59 GAS strains (m = 40) collected during 2000–2009 by the Active Bacterial Core surveillance (ABCs), a core component of the Centers for Disease Control and Prevention Emerging Infections Programs network. ABCs, an active, laboratory- and population-based surveillance system operating in 10 geographically disparate sites across the United States, represents a population of ≈32 million persons under surveillance for invasive GAS infections (www.cdc.gov/abcs/methodology/surv-pop.html).