Characterization of NAD salvage pathways and their role in virulence in Streptococcus pneumoniae.

作者: Michael D. L. Johnson , Tina H. Dao , Haley Echlin , Jason W. Rosch

DOI: 10.1099/MIC.0.000164

关键词: Nicotinamide mononucleotideBiochemistryNicotinamideNAD salvageNicotinamide ribosidePathogenVirulenceBiologyNAD+ kinaseStreptococcus pneumoniaeMicrobiology

摘要: NAD is a necessary cofactor present in all living cells. Some bacteria cannot de novo synthesize and must use the salvage pathway to import niacin or nicotinamide riboside via substrate importers NiaX PnuC, respectively. Although homologues of these two their substrates have been identified other organisms, limited data exist Streptococcus pneumoniae, specifically, on its effect overall virulence. Here, we sought characterize specificity PnuC Str. pneumoniae TIGR4 contribution proteins virulence pathogen. binding affinity each importer for mononucleotide may overlap, found specifically nicotinic acid, be primarily responsible import. Furthermore, pnuC mutant completely attenuated during both intranasal intratracheal infections mice. Taken together, findings underscore importance pneumococcal pathogenesis indicate that could potentially viable small-molecule therapeutic target alleviate disease progression host.

参考文章(40)
Robert M. Horton, Zeling Cai, Steffan N. Ho, Larry R. Pease, Gene Splicing by Overlap Extension: Tailor-Made Genes Using the Polymerase Chain Reaction BioTechniques. ,vol. 8, pp. 528- 535 ,(2013) , 10.2144/000114017
J SCHMIDTBRAUNS, Is a NAD pyrophosphatase activity necessary for type b multiplication in the blood stream? International Journal of Medical Microbiology. ,vol. 291, pp. 219- 225 ,(2001) , 10.1078/1438-4221-00122
M. P. SPECTOR, J. M. HILL, E. A. HOLLEY, J. W. FOSTER, Genetic characterization of pyridine nucleotide uptake mutants of Salmonella typhimurium. Microbiology. ,vol. 131, pp. 1313- 1322 ,(1985) , 10.1099/00221287-131-6-1313
Mark Herbert, Elizabeta Sauer, Graeme Smethurst, Anita Kraiβ, Anna-Karina Hilpert, Joachim Reidl, Nicotinamide Ribosyl Uptake Mutants in Haemophilus influenzae Infection and Immunity. ,vol. 71, pp. 5398- 5401 ,(2003) , 10.1128/IAI.71.9.5398-5401.2003
Masahiko S. Satoh, Tomas Lindahl, Role of poly(ADP-ribose) formation in DNA repair Nature. ,vol. 356, pp. 356- 358 ,(1992) , 10.1038/356356A0
Elizabeta Sauer, Melisa Merdanovic, Anne Price Mortimer, Gerhard Bringmann, Joachim Reidl, PnuC and the Utilization of the Nicotinamide Riboside Analog 3-Aminopyridine in Haemophilus influenzae Antimicrobial Agents and Chemotherapy. ,vol. 48, pp. 4532- 4541 ,(2004) , 10.1128/AAC.48.12.4532-4541.2004