作者: Michael D. L. Johnson , Tina H. Dao , Haley Echlin , Jason W. Rosch
DOI: 10.1099/MIC.0.000164
关键词: Nicotinamide mononucleotide 、 Biochemistry 、 Nicotinamide 、 NAD salvage 、 Nicotinamide riboside 、 Pathogen 、 Virulence 、 Biology 、 NAD+ kinase 、 Streptococcus pneumoniae 、 Microbiology
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.