TheStreptococcus pyogenesmannose phosphotransferase system (Man-PTS) influences antimicrobial activity and niche-specific nasopharyngeal infection
Authors: Marple Amanda C. , Shannon Blake A. , Rishi Aanchal , Estafanos Lana , Armstrong Brent D. , Oropeza Veronica Guariglia , Tuffs Stephen W. , McCormick John K. 
Published: October 2024

ABSTRACTStreptococcus pyogenesis a human-adapted pathogen that causes a variety of infections including pharyngitis and skin infections, and although this bacterium produces many virulence and host colonization factors, howS. pyogenescompetes with the host microbiota is not well understood. Here we detected antimicrobial activity produced fromS. pyogenesMGAS8232 that was able to prevent the growth ofMicrococcus luteus. This activity was produced when cells were grown in 5% CO2and in M17 media supplemented with galactose; however, evaluation of the phenotype with the addition of alternative sugars coupled with genome sequencing experiments revealed the antimicrobial phenotype was not related to classical bacteriocins. To further determine genes involved in the production of this activity, a transposon mutant library inS. pyogenesMGAS8232 was generated. The transposon screen identified the mannose phosphotransferase system (Man-PTS), a major sugar transporter inS. pyogenes, as important for the antimicrobial phenotype. Additional loss-of-function transposon mutants linked to the antimicrobial activity were identified to also be involved in alternative sugar utilization and additionally, the Man-PTS was also further identified from a secondary mutation in a bacteriocin operon mutant. Sugar utilization profiles in all the Man-PTS mutants demonstrated that galactose, mannose, and N-acetylglucosamine utilization was impaired in different Man-PTS mutants.In vitroRNA-seq experiments in high and low glucose concentrations further identified the Man-PTS as a glucose transporter; however, there was no transcriptional regulators or virulence factors affected with the loss of the Man-PTS. A clean deletion in the Man-PTS demonstrated defects in a mouse model of nasopharyngeal infection. Overall, the ability ofS. pyogenesto utilize alternative sugars presented by glycans seems to play a role in acute infection and interactions with the endogenous microbial population existing in the nasopharynx.IMPORTANCEStreptococcus pyogenescauses a wide range of infections and is responsible for over 500,000 deaths per year due to invasive infections and post-infection sequelae. The most common clinical manifestation ofS. pyogeneshowever are acute infections such as pharyngitis or impetigo.S. pyogenescan adapt to its environment through alternative sugar metabolism and in this study, we identified an antimicrobial phenotype that was not bacteriocin-related but a by-product of alternative sugar metabolism. Evidently, the mannose phosphotransferase system, a well-studied sugar transporter, was involved in production of the antimicrobial, and was also important forS. pyogenesto utilize alternative sugars and establish nasopharyngeal infection, but not skin infection. Overall, this study identified potential strategies used byS. pyogenesfor interactions with the endogenous microbiota and further elucidated the importance of sugar metabolism in acute infection.