Molecular characterization of group A Streptococcus maltodextrin catabolism and its role in pharyngitis.
We previously demonstrated that the cell-surface lipoprotein MalE contributes to GAS maltose/maltodextrin utilization, but MalE inactivation does not completely abrogate GAS catabolism of maltose or maltotriose. Using a genome-wide approach, we identified the GAS phosphotransferase system (PTS) responsible for non-MalE maltose/maltotriose transport. This PTS is encoded by an open reading frame (M5005_spy1692) previously annotated as ptsG based on homology with the glucose PTS in Bacillus subtilis. Genetic inactivation of M5005_spy1692 significantly reduced transport rates of radiolabelled maltose and maltotriose, but not glucose, leading us to propose its reannotation as malT for maltose transporter. The DeltamalT, DeltamalE and DeltamalE:malT strains were significantly attenuated in their growth in human saliva and in their ability to catabolize alpha-glucans digested by purified human salivary alpha-amylase. Compared with wild-type, the three isogenic mutant strains were significantly impaired in their ability to colonize the mouse oropharynx. Finally, we discovered that the transcript levels of maltodextrin utilization genes are regulated by competitive binding of the maltose repressor MalR and catabolite control protein A. These data provide novel insights into regulation of the GAS maltodextrin genes and their role in GAS host-pathogen interaction, thereby increasing the understanding of links between nutrient acquisition and virulence in common human pathogens.
Shelburne
Samuel A
SA
Section of Infectious Diseases, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
Keith
David B
DB
Davenport
Michael T
MT
Horstmann
Nicola
N
Brennan
Richard G
RG
Musser
James M
JM
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D015169:Colony Count, Microbial; D017353:Gene Deletion; D020869:Gene Expression Profiling; D005936:Glucans / Q000378:metabolism; D006801:Humans; D008320:Maltose / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D010612:Pharyngitis / Q000382:microbiology*; D010614:Pharynx / Q000382:microbiology; D010731:Phosphoenolpyruvate Sugar Phosphotransferase System / Q000235:genetics / Q000378:metabolism*; D011134:Polysaccharides / Q000378:metabolism*; D012463:Saliva / Q000382:microbiology; D013297:Streptococcus pyogenes / Q000254:growth & development / Q000378:metabolism* / Q000472:pathogenicity*; D014312:Trisaccharides / Q000378:metabolism
D001426:Bacterial Proteins; D005936:Glucans; D011134:Polysaccharides; D014312:Trisaccharides; C008317:maltotriose; D008320:Maltose; C008315:maltodextrin; D010731:Phosphoenolpyruvate Sugar Phosphotransferase System; C031629:phosphoenolpyruvate-glucose phosphotransferase