title: Characterization of NAD salvage pathways and their role in virulence in Streptococcus pneumoniae.
abstract: NAD is a necessary cofactor present in all living cells. Some bacteria cannot de novo synthesize NAD and must use the salvage pathway to import niacin or nicotinamide riboside via substrate importers NiaX and PnuC, respectively. Although homologues of these two importers and their substrates have been identified in other organisms, limited data exist in Streptococcus pneumoniae, specifically, on its effect on overall virulence. Here, we sought to characterize the substrate specificity of NiaX and PnuC in Str. pneumoniae TIGR4 and the contribution of these proteins to virulence of the pathogen. Although binding affinity of each importer for nicotinamide mononucleotide may overlap, we found NiaX to specifically import nicotinamide and nicotinic acid, and PnuC to be primarily responsible for nicotinamide riboside import. Furthermore, a pnuC mutant is completely attenuated during both intranasal and intratracheal infections in mice. Taken together, these findings underscore the importance of substrate salvage in pneumococcal pathogenesis and indicate that PnuC could potentially be a viable small-molecule therapeutic target to alleviate disease progression in the host.
authors: Department of Infectious Diseases, St Jude Children's Research Hospital, Memphis, TN 38105-3678, USA.
authors: Michael D L
authors: MD
authors: Johnson
authors: Department of Infectious Diseases, St Jude Children's Research Hospital, Memphis, TN 38105-3678, USA.
authors: Haley
authors: H
authors: Echlin
authors: Department of Infectious Diseases, St Jude Children's Research Hospital, Memphis, TN 38105-3678, USA.
authors: Tina H
authors: TH
authors: Dao
authors: Department of Infectious Diseases, St Jude Children's Research Hospital, Memphis, TN 38105-3678, USA.
authors: Jason W
authors: JW
authors: Rosch
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D017353:Gene Deletion; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009243:NAD / Q000378:metabolism*; D011008:Pneumococcal Infections / Q000382:microbiology / Q000473:pathology; D013296:Streptococcus pneumoniae / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D013379:Substrate Specificity; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D026901:Membrane Transport Proteins; D037521:Virulence Factors; D009243:NAD