Unraveling Streptococcus pyogenes Carriage: Genomic and Transcriptomic Insights from Acute and Post-Treatment Phases

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Abstract The carrier state of Streptococcus pyogenes (Group A Streptococcus, GAS), is defined by the presence of the organism without symptoms or an immune response. Carriage poses challenges for clinical management and contributes to transmission in the community. Prior studies suggest genetic and phenotypic differences between isolates from symptomatic (acute) infections and those from carriers, yet comprehensive genomic and transcriptomic analyses of naturally acquired human GAS carriage have been lacking. In this study, we collected longitudinal samples from individuals before and after antibiotic treatment for acute pharyngitis, performing whole genome sequencing and RNA-seq on selected isolates. This is the first report of transcriptional profiling of GAS directly from human derived oropharyngeal swabs. Genomic analysis revealed no consistent carrier-specific genotypes, and in vitro assays showed no major differences in biofilm formation or antibiotic susceptibility between carrier and acute isolates. Transcriptional profiling from oropharyngeal swabs identified distinct gene expression patterns when comparing the acute infection and post-treatment carriage phases, although early acute expression profiles did not predict treatment failure. These findings suggest that GAS carriage is likely influenced by conserved bacterial traits as well as host factors, advancing our understanding of GAS persistence and transmission. Summary Longitudinal samples were collected from individuals before and after treatment for acute Group A Streptococcal pharyngitis. Whole genome sequencing and RNA-seq was performed on selected isolates. This is the first report of transcriptional profiling of GAS directly from human oropharyngeal swabs. Distinct gene expression patterns were observed when comparing the acute infection and post-treatment carriage.

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