Whole genome sequencing of group A Streptococcus (GAS) populations is challenging the traditional view of the GAS genome consisting of a stable unvarying core genome and an accessory genome controlled by mobile genetic elements (MGEs). We, and others, have previously demonstrated that horizontal gene transfer in the core genome can occur, leading to the emergence of new variants that drive GAS population shifts.
Genomic analysis of GAS isolates dating from the pre-antibiotic era and modern isolates identified hot spots for recombination in a number of different emm-types. One identified region was the NADase/SLO locus. This locus has been associated with the success of modern emm1 and the new variant of emm89 lineages, where recombination events have led to variants with high NADase and SLO expression. Recombination of this locus is not however restricted to emm1 and emm89, and has also produced lineages of emm28, emm87, emm75 and emm76 with enhanced toxin production. In some cases, like emm89, these lineages are also acapsular. A modern UK emm75 lineage carried an NADase/SLO locus almost identical to that found in modern emm1 and the emergent emm89 lineages, likely gained through recombination as historical emm75 strains had a different NADase/SLO locus with features of low toxin expression. The dominance of the NADase/SLO locus among recombination hot spots underlines its likely role in the evolution of GAS in the modern era, in response to environmental and host pressures that are as yet unknown but could include antimicrobials and disinfectants.