title: Maltodextrin utilization plays a key role in the ability of group A Streptococcus to colonize the oropharynx.
abstract: Analysis of multiple group A Streptococcus (GAS) genomes shows that genes encoding proteins involved in carbohydrate utilization comprise some 15% of the core GAS genome. Yet there is a limited understanding of how carbohydrate utilization contributes to GAS pathogenesis. Previous genome-wide GAS studies led us to a focused investigation of MalE, a putative maltodextrin-binding protein. Analysis of 28 strains of 22 distinct M protein serotypes showed that MalE is highly conserved among diverse GAS strains. malE transcript levels were significantly increased during growth in human saliva compared to growth in a chemically defined glucose-containing medium or a nutrient-rich medium. MalE was accessible to antibody binding, indicating that it is expressed on the GAS cell surface. Moreover, growth in human saliva appeared to increase MalE surface expression compared to growth in a nutrient-rich medium. Analysis of a delta malE isogenic mutant strain revealed decreased growth in human saliva compared to wild-type GAS. Radiolabeled carbohydrate binding assays showed that MalE was required for the binding of maltose but not glucose. The delta malE isogenic mutant strain colonized a lower percentage of GAS-challenged mice compared to wild-type and genetically complemented strains. Furthermore, decreased numbers of CFU were recovered from mice infected with the delta malE strain compared to those infected with wild-type GAS. These data demonstrate that maltodextrin acquisition is likely to be a key factor in the ability of GAS to successfully infect the oropharynx. Further investigation into carbohydrate transport and metabolism pathways may yield novel insights into GAS pathogenesis.
authors.affiliation: Section of Infectious Diseases, Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Samuel A
authors.initials: SA
authors.lastname: Shelburne
authors.forename: Paul
authors.initials: P
authors.lastname: Sumby
authors.forename: Izabela
authors.initials: I
authors.lastname: Sitkiewicz
authors.forename: Nnaja
authors.initials: N
authors.lastname: Okorafor
authors.forename: Chanel
authors.initials: C
authors.lastname: Granville
authors.forename: Payal
authors.initials: P
authors.lastname: Patel
authors.forename: Jovanka
authors.initials: J
authors.lastname: Voyich
authors.forename: Richard
authors.initials: R
authors.lastname: Hull
authors.forename: Frank R
authors.initials: FR
authors.lastname: DeLeo
authors.forename: James M
authors.initials: JM
authors.lastname: Musser
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D003470:Culture Media; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D051379:Mice; D009154:Mutation; D009960:Oropharynx / Q000382:microbiology*; D011134:Polysaccharides / Q000378:metabolism*; D012463:Saliva / Q000382:microbiology; D013297:Streptococcus pyogenes / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D003470:Culture Media; D011134:Polysaccharides; C008315:maltodextrin