A member of the second carbohydrate uptake subfamily of ATP-binding cassette transporters is responsible for ribonucleoside uptake in Streptococcus mutans.
Streptococcus mutans has a significant number of transporters of the ATP-binding cassette (ABC) superfamily. Members of this superfamily are involved in the translocation of a diverse range of molecules across membranes. However, the functions of many of these members remain unknown. We have investigated the role of the single S. mutans representative of the second subfamily of carbohydrate uptake transporters (CUT2) of the ABC superfamily. The genetic context of genes encoding this transporter indicates that it may have a role in ribonucleoside scavenging. Inactivation of rnsA (ATPase) or rnsB (solute binding protein) resulted in strains resistant to 5-fluorocytidine and 5-fluorouridine (toxic ribonucleoside analogues). As other ribonucleosides including cytidine, uridine, adenosine, 2-deoxyuridine, and 2-deoxycytidine protected S. mutans from 5-fluorocytidine and 5-fluorouridine toxicity, it is likely that this transporter is involved in the uptake of these molecules. Indeed, the rnsA and rnsB mutants were unable to transport [2-(14)C]cytidine or [2-(14)C]uridine and had significantly reduced [8-(14)C]adenosine uptake rates. Characterization of this transporter in wild-type S. mutans indicates that it is a high-affinity (K(m) = 1 to 2 muM) transporter of cytidine, uridine, and adenosine. The inhibition of [(14)C]cytidine uptake by a range of structurally related molecules indicates that the CUT2 transporter is involved in the uptake of most ribonucleosides, including 2-deoxyribonucleosides, but not ribose or nucleobases. The characterization of this permease has directly shown for the first time that an ABC transporter is involved in the uptake of ribonucleosides and extends the range of substrates known to be transported by members of the ABC transporter superfamily.
Webb
Alexander J
AJ
Microbiology, King's College London Dental Institute, London, United Kingdom.
Hosie
Arthur H F
AH
D018528:ATP-Binding Cassette Transporters / Q000502:physiology*; D000241:Adenosine / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D050260:Carbohydrate Metabolism; D003562:Cytidine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D024881:Drug Resistance, Bacterial; D006801:Humans; D009154:Mutation; D012263:Ribonucleosides / Q000378:metabolism*; D013290:Streptococcal Infections / Q000382:microbiology; D013295:Streptococcus mutans / Q000187:drug effects / Q000378:metabolism*; D014529:Uridine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology
D018528:ATP-Binding Cassette Transporters; D001426:Bacterial Proteins; D012263:Ribonucleosides; C001943:5-fluorouridine; D003562:Cytidine; D000251:Adenosine Triphosphatases; D000241:Adenosine; C007745:5-fluorocytidine; D014529:Uridine