Contribution of AmyA, an extracellular α-glucan degrading enzyme, to group A streptococcal host-pathogen interaction

α-Glucans such as starch and glycogen are abundant in the human oropharynx, the main site of group A Streptococcus (GAS) infection. However, the role in pathogenesis of GAS extracellular a-glucan binding and degrading enzymes is unknown. The serotype M1 GAS genome encodes two extracellular proteins putatively involved in a-glucan binding and degradation; pulA encodes a cell wall anchored pullulanase and amyA encodes a freely secreted putative cyclomaltodextrin a-glucanotransferase. Genetic inactivation of amyA, but not pulA, abolished GAS α-glucan degradation. The AamyA strain had a slower rate of translocation across human pharyngeal epithelial cells. Consistent with this finding, the AamyA strain was less virulent following mouse mucosal challenge. Recombinant AmyA degraded α-glucans into β- cyclomaltodextrins that reduced pharyngeal cell transepithelial resistance, providing a physiologic explanation for the observed transepithelial migration phenotype. Higher amyA transcript levels were present in serotype M1 GAS strains causing invasive infection compared with strains causing pharyngitis. GAS proliferation in a defined a-glucan-containing medium was dependent on the presence of human salivary a-amylase. These data delineate the molecular mechanisms by which a-glucan degradation contributes to GAS host-pathogen interaction, including how GAS uses human salivary a-amylase for its own metabolic benefit.