Assimilation of NAD+ precursors in Candida glabrata

Biao Ma, Shih Jung Pan, Margaret L. Zupancic, Brendan P. Cormack

Research output: Contribution to journalArticlepeer-review

Abstract

The yeast pathogen Candida glabrata is a nicotinamide adenine dinucleotide (NAD+) auxotroph and its growth depends on the environmental supply of vitamin precursors of NAD+. C. glabrata salvage pathways defined in this article allow NAD+ to be synthesized from three compounds - nicotinic acid (NA), nicotinamide (NAM) and nicotinamide riboside (NR). NA is salvaged through a functional Preiss-Handler pathway. NAM is first converted to NA by nicotinamidase and then salvaged by the Preiss-Handler pathway. Salvage of NR in C. glabrata occurs via two routes. The first, in which NR is phosphorylated by the NR kinase Nrk1, is independent of the Preiss-Handler pathway. The second is a novel pathway in which NR is degraded by the nucleosidases Pnp1 and Urh1, with a minor role for Meu1, and ultimately converted to NAD+ via the nicotinamidase Pnc1 and the Preiss-Handler pathway. Using C. glabrata mutants whose growth depends exclusively on the external NA or NR supply, we also show that C. glabrata utilizes NR and to a lesser extent NA as NAD+ sources during disseminated infection.

Original languageEnglish (US)
Pages (from-to)14-25
Number of pages12
JournalMolecular Microbiology
Volume66
Issue number1
DOIs
StatePublished - Oct 2007

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

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