title: ManLMN is a glucose transporter and central metabolic regulator in Streptococcus pneumoniae.
abstract: Streptococcus pneumoniae is a common colonizer of the human nasopharynx and a leading cause of bacterial pneumonia and otitis media, among other invasive diseases. During both colonization and invasive disease S. pneumoniae ferments host-derived carbohydrates as its primary means of generating energy. This pathogen is adept at transporting and metabolizing a wide variety of carbohydrates. We found the highly conserved PTS ManLMN contributes to growth on glucose and is also essential for growth on a variety of nonpreferred carbohydrates, suggesting it is a multisubstrate transporter. Exploration of this phenotype revealed ManLMN is required for inducing expression of downstream metabolic genes in response to carbohydrate stimuli. We further demonstrate that ManLMN's role as a constitutively expressed transporter is likely unique and integral to pneumococcus's strategy of carbon catabolite repression (CCR). Using a selection for suppressors, we explored how ManLMN is integrated into the CCR regulatory framework in S. pneumoniae. We identified two hypothetical small proteins and the virulence regulator SmrC as potential mediators of CCR in connection with ManLMN. Characterization of these two hypothetical proteins revealed they influence transcriptional regulation of carbohydrate transporters. We propose a model unifying these observations in which ManLMN is a versatile surveyor of available carbohydrates in S. pneumoniae.
authors.affiliation: Program in Molecular Microbiology, Sackler School of Graduate Biomedical Sciences, Howard Hughes Medical Institute, and Department of Molecular Biology and Microbiology, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA, 02111, USA.
authors.forename: Eleanor
authors.initials: E
authors.lastname: Fleming
authors.affiliation: Program in Molecular Microbiology, Sackler School of Graduate Biomedical Sciences, Howard Hughes Medical Institute, and Department of Molecular Biology and Microbiology, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA, 02111, USA. andrew.camilli@tufts.edu.
authors.forename: Andrew
authors.initials: A
authors.lastname: Camilli
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism; D001692:Biological Transport; D050260:Carbohydrate Metabolism; D057465:Catabolite Repression; D004268:DNA-Binding Proteins / Q000378:metabolism; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009876:Operon; D010731:Phosphoenolpyruvate Sugar Phosphotransferase System / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism; D013296:Streptococcus pneumoniae / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D051246:Glucose Transport Proteins, Facilitative; D012097:Repressor Proteins; D010731:Phosphoenolpyruvate Sugar Phosphotransferase System