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Volume 161, Issue 11

Characterization of NAD salvage pathways and their role in virulence in Free

Abstract

NAD is a necessary cofactor present in all living cells. Some bacteria cannot 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 , specifically, on its effect on overall virulence. Here, we sought to characterize the substrate specificity of NiaX and PnuC in 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 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.

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© 2015 The Authors
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2015-11-01
2024-04-24
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Characterization of NAD salvage pathways and their role in virulence in Streptococcus pneumoniae
Microbiology 161, 2127 (2015); https://doi.org/10.1099/mic.0.000164
/content/journal/micro/10.1099/mic.0.000164
/content/journal/micro/10.1099/mic.0.000164
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