Increased pilus production conferred by a naturally occurring mutation alters host-pathogen interaction in favor of carriage in Streptococcus pyogenes


Anthony R. Flores, Randall J. Olsen, Concepcion Cantu, Kyler B. Pallister, Fermin E. Guerra, Jovanka M. Voyich, James M. Musser


Infection and Immunity


Studies of the human pathogen group A Streptococcus (GAS) define the carrier phenotype as increased ability to adhere to and persist on epithelial surfaces and decreased ability to cause disease. We tested the hypothesis that a single amino acid change (Arg135Gly) in a highly conserved sensor kinase (LiaS) of a poorly defined GAS regulatory system contributes to a carrier phenotype through increased pilus production. When introduced into an emm serotype-matched invasive strain, the carrier allele (liaSR135G) recapitulated a carrier phenotype defined by increased ability to adhere to mucosal surfaces and decreased ability to cause disease. Gene transcript analyses revealed that the liaS mutation significantly altered transcription of the genes encoding pilus when in the presence of bacitracin. Elimination of pilus production in the isogenic carrier mutant decreased ability to colonize the mouse nasopharynx, adhere to and be internalized by cultured human epithelial cells, and restored a virulence phenotype in a mouse model of necrotizing fasciitis. We also observed significantly reduced survival of the isogenic carrier mutant compared to the parental invasive strain after exposure to human neutrophils. Elimination of pilus in the isogenic carrier mutant increased neutrophil survival to the parental invasive strain level. Together, our data demonstrate that the carrier mutation (liaSR135G) affects pilus expression. Our data suggest new mechanisms of pilus gene regulation in GAS and differs from the enhanced invasiveness associated with increased pilus production in other bacterial pathogens.



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