Regulation of Polysaccharide Utilization Contributes to the Persistence of Group A Streptococcus in the Oropharynx

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Abstract
Group A Streptococcus (GAS) genes that encode proteins putatively involved in polysaccharide utilization show growth phase-dependent expression in human saliva. We sought to determine whether the putative polysaccharide transcriptional regulator MalR influences the expression of such genes and whether MalR helps GAS infect the oropharynx. Analysis of 32 strains of 17 distinct M protein serotypes revealed that MalR is highly conserved across GAS strains. malR transcripts were detectable in patients with GAS pharyngitis, and the levels increased significantly during growth in human saliva compared to the levels during growth in glucose-containing or nutrient-rich media. To determine if MalR influenced the expression of polysaccharide utilization genes, we compared the transcript levels of eight genes encoding putative polysaccharide utilization proteins in the parental serotype M1 strain MGAS5005 and its Δ malR isogenic mutant derivative. The transcript levels of all eight genes were significantly increased in the Δ malR strain compared to the parental strain, especially during growth in human saliva. Following experimental infection, the Δ malR strain persistently colonized the oropharynx in significantly fewer mice than the parental strain colonized, and the numbers of Δ malR strain CFU recovered were significantly lower than the numbers of the parental strain CFU recovered. These data led us to conclude that MalR influences the expression of genes putatively involved in polysaccharide utilization and that MalR contributes to the persistence of GAS in the oropharynx.

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