Cluster of Fatal Group A Streptococcal emm87 Infections in a Single Family: Molecular Basis for Invasion and Transmission

Hypervirulent disease due to group A Streptococcus (GAS) can result from strains with mutations that enhance virulence gene expression but reduce subsequent transmission. We used whole-genome sequencing to investigate intrafamilial spread among 4 siblings of infection due to a hypervirulent GAS strain that resulted in a fatality. All invasive and pharyngeal GAS isolates had an identical mutation in a gene encoding a key regulatory protein that yielded a hyperinvasive phenotype. These data challenge the prevailing theory of reduced transmission induced by mutations that lead to hypervirulent GAS by showing that spread of hypervirulent GAS may lead to clusters of invasive disease.