Background: The antigenic and structural diversity of the GAS cell surface is largely conferred via proteins encoded by the M- and FCT-regions. Nearly all GAS infections (>99%) lead to pharyngitis or impetigo.
Methods: Methods include global strain sampling for diversity (N=628), WGS and bioinformatics.
Results: A pilin genotyping scheme based on pilin adhesin (pilA) and backbone (pilB) genes was developed using cluster analysis. From a global collection of 628 genomes (169 emm types), 98 pilin types were identified. The relationships between emm and pilin types reveal a history of extensive recombinational exchange among GAS, wherein 379 unique combinations of emm-pilin types approximate the concept of ‘strain.’ A meta-analysis of 44 population-based surveys for pharyngitis and impetigo isolates shows relative ratios of pharyngitis to impetigo of 4.9, 0.12 (reciprocal, 8.6) and 1.3 for emm patterns A-C (throat specialists), D (skin specialists) and E (generalists), respectively. Inferences on pilin type, based on emm type, provide a rough sketch of the population biology of GAS: Some pilin types are strongly associated with pharyngitis (pil001/pil002/pil004/pill006/pil012/pil028), and others with impetigo (pil042/pil053/pil081/pil114). Six clusters of the pilA adhesin (nt80_8/12/14-17; associated with 54 emm types), combined with an emm-encoded plasminogen-binding domain, display a 10-20-fold preference for impetigo over pharyngitis.
Conclusions: Global population genomics can be used to develop hypotheses on the multifactorial basis for tissue-specific adaptations. Opposing selection pressures, mediated via host immunity, leave an imprint on the population genetic structure of GAS and provide insights on vaccine design. The pilin genotyping scheme is available at www.pubmlst.org/spyogenes.