Identifying genetic determinants of Streptococcus pyogenes-host interactions in a murine intact skin infection model

Streptococcus pyogenes is an obligate human pathobiont associated with many disease states. Here, we present a model of S. pyogenes infection using intact murine epithelium. We were able to perform RNA sequencing to evaluate genetic changes undertaken by both the bacterium and host at 5 and 24 h post-infection. Analysis of these genomic data demonstrate that S. pyogenes undergoes genetic adaptation to successfully infect the murine epithelium, including changes to metabolism and activation of the Rgg2/Rgg3 quorum-sensing (QS) system. Subsequent experiments demonstrate that an intact Rgg2/Rgg3 QS cascade is necessary to establish a stable superficial skin infection. QS cascade activation results in increased murine morbidity and bacterial burden on the skin. This phenotype is associated with gross changes to the murine skin and with evidence of inflammation. These experiments offer a method to investigate S. pyogenes-epithelial interactions and demonstrate that a well-studied QS pathway is critical to a persistent infection. [Display omitted] •These finding demonstrate an intact skin infection in mice by S. pyogenes•RNA-seq of S. pyogenes during skin infection shows significant genetic adaptation•The Rgg2/Rgg3 quorum-sensing system is induced during skin infection•The Rgg2/Rgg3 quorum-sensing system is necessary for sustained skin infection Wilkening et al. present a model of murine skin infection by Streptococcus pyogenes. Dual RNA sequencing was used to assess bacterial and murine adaptation to infection. Subsequent studies demonstrate that the Rgg2/Rgg3 quorum-sensing system is induced during infection and is necessary for sustained infection, leading to increased host morbidity.