Global spread of Streptococcus pyogenes A genomics-supported narrative review

: Group A Streptococcus (GAS) has recently re-emerged as a leading cause of both mild and severe invasive infections worldwide, with recent upsurges in invasive disease among children and adults. Notwithstanding a partial synchronicity with the COVID-19 pandemic, this rapid global dissemination of more virulent GAS lineages has been promptly detected, as well as the molecular shifts underlying the observed changes in clinical patterns. Whole-genome sequencing (WGS)-based genomic epidemiology allowed us to gain relevant insights into this upsurge as it was happening. This review integrates the canonical research publication-based approach with genomic data and metadata and identifies a subset of genomic clusters playing a major role in invasive-GAS (iGAS) infections worldwide, which were named as Global Pathogenic Lineages (GPLs). The four GPLs broadly coincide with five Sequence Types (STs): GPL1 with ST28, GPL2 with ST15 and ST315, GPL3 with ST52 and GPL4 with ST39. While non-GPLs clusters maintain a baseline reservoir of antimicrobial-resistance and virulence genes, GPLs show varying but noteworthy resistance profiles and are frequent causes of iGAS. The integration of WGS into routine diagnostics procedures is a forthcoming improvement, aimed not only at informing tailored therapy and implementing infection control strategies, but also to perform continuous surveillance. Ongoing WGS in clinical microbiology, as a matter of fact, will provide unparalleled insights into lineage emergence, transmission dynamics, and the geographic clustering of virulence and resistance determinants.