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

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

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

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 smallmolecule therapeutic target to alleviate disease progression in the host.

Original languageEnglish (US)
Pages (from-to)2127-2136
Number of pages10
JournalMicrobiology (United Kingdom)
Volume161
Issue number11
DOIs
StatePublished - Nov 2015
Externally publishedYes

ASJC Scopus subject areas

  • Microbiology

Fingerprint

Dive into the research topics of 'Characterization of NAD salvage pathways and their role in virulence in Streptococcus pneumoniae'. Together they form a unique fingerprint.

Cite this