title: Contribution of AmyA, an extracellular alpha-glucan degrading enzyme, to group A streptococcal host-pathogen interaction.
abstract: alpha-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 alpha-glucan binding and degrading enzymes is unknown. The serotype M1 GAS genome encodes two extracellular proteins putatively involved in alpha-glucan binding and degradation; pulA encodes a cell wall anchored pullulanase and amyA encodes a freely secreted putative cyclomaltodextrin alpha-glucanotransferase. Genetic inactivation of amyA, but not pulA, abolished GAS alpha-glucan degradation. The DeltaamyA strain had a slower rate of translocation across human pharyngeal epithelial cells. Consistent with this finding, the DeltaamyA strain was less virulent following mouse mucosal challenge. Recombinant AmyA degraded alpha-glucans into beta-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 alpha-glucan-containing medium was dependent on the presence of human salivary alpha-amylase. These data delineate the molecular mechanisms by which alpha-glucan degradation contributes to GAS host-pathogen interaction, including how GAS uses human salivary alpha-amylase for its own metabolic benefit.
authors.affiliation: Department of Infectious Diseases, MD Anderson Cancer Center, Houston, TX 77030, USA.Section of Infectious Diseases, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.Center for Molecular and Translational Human Infectious Diseases Research, The Methodist Hospital Research Institute, and Department of Pathology, The Methodist Hospital, Houston, TX 77030, USA.
authors.forename: Samuel A
authors.initials: SA
authors.lastname: Shelburne Iii
authors.affiliation: Department of Infectious Diseases, MD Anderson Cancer Center, Houston, TX 77030, USA.Section of Infectious Diseases, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.Center for Molecular and Translational Human Infectious Diseases Research, The Methodist Hospital Research Institute, and Department of Pathology, The Methodist Hospital, Houston, TX 77030, USA.
authors.forename: David B
authors.initials: DB
authors.lastname: Keith
authors.affiliation: Department of Infectious Diseases, MD Anderson Cancer Center, Houston, TX 77030, USA.Section of Infectious Diseases, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.Center for Molecular and Translational Human Infectious Diseases Research, The Methodist Hospital Research Institute, and Department of Pathology, The Methodist Hospital, Houston, TX 77030, USA.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Davenport
authors.affiliation: Department of Infectious Diseases, MD Anderson Cancer Center, Houston, TX 77030, USA.Section of Infectious Diseases, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.Center for Molecular and Translational Human Infectious Diseases Research, The Methodist Hospital Research Institute, and Department of Pathology, The Methodist Hospital, Houston, TX 77030, USA.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Beres
authors.affiliation: Department of Infectious Diseases, MD Anderson Cancer Center, Houston, TX 77030, USA.Section of Infectious Diseases, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.Center for Molecular and Translational Human Infectious Diseases Research, The Methodist Hospital Research Institute, and Department of Pathology, The Methodist Hospital, Houston, TX 77030, USA.
authors.forename: Ronan K
authors.initials: RK
authors.lastname: Carroll
authors.affiliation: Department of Infectious Diseases, MD Anderson Cancer Center, Houston, TX 77030, USA.Section of Infectious Diseases, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.Center for Molecular and Translational Human Infectious Diseases Research, The Methodist Hospital Research Institute, and Department of Pathology, The Methodist Hospital, Houston, TX 77030, USA.
authors.forename: James M
authors.initials: JM
authors.lastname: Musser
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D003505:Cyclodextrins / Q000096:biosynthesis; D005260:Female; D005816:Genetic Complementation Test; D005936:Glucans / Q000378:metabolism; D005964:Glucosyltransferases / Q000235:genetics / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D051379:Mice; D016254:Mutagenesis, Insertional; D009154:Mutation; D010612:Pharyngitis / Q000382:microbiology; D012329:RNA, Bacterial / Q000235:genetics; D013290:Streptococcal Infections / Q000382:microbiology; D013297:Streptococcus pyogenes / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D003505:Cyclodextrins; D005936:Glucans; D012329:RNA, Bacterial; D005964:Glucosyltransferases; C019963:cyclomaltodextrin glucanotransferase