Puerperal sepsis, a major cause of death of young women in Europe in the 1800s, was due predominantly to the gram-positive pathogen group A Streptococcus Studies conducted during past decades have shown that serotype M28 strains are the major group A Streptococcus organisms responsible for many of these infections. To begin to increase our understanding of their enrichment in puerperal sepsis, we sequenced the genome of a genetically representative strain. This strain has genes encoding a novel array of prophage virulence factors, cell-surface proteins, and other molecules likely to contribute to host-pathogen interactions. Importantly, genes for 7 inferred extracellular proteins are encoded by a 37.4-kb foreign DNA element that is shared with group B Streptococcus and is present in all serotype M28 strains. Proteins encoded by the 37.4-kb element were expressed extracellularly and in human infections. Acquisition of foreign genes has helped create a disease-specialist clone of this pathogen