Assimilation of NAD(+) precursors in Candida glabrata

Mol Microbiol. 2007 Oct;66(1):14-25. doi: 10.1111/j.1365-2958.2007.05886.x. Epub 2007 Aug 28.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Candida glabrata / genetics
  • Candida glabrata / growth & development
  • Candida glabrata / metabolism*
  • Gene Deletion
  • Metabolic Networks and Pathways*
  • Mice
  • N-Glycosyl Hydrolases / genetics
  • N-Glycosyl Hydrolases / metabolism
  • NAD / biosynthesis*
  • Niacin / metabolism
  • Niacinamide / analogs & derivatives
  • Niacinamide / metabolism
  • Nicotinamidase / genetics
  • Nicotinamidase / metabolism
  • Phosphotransferases (Alcohol Group Acceptor) / genetics
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism

Substances

  • nicotinamide-beta-riboside
  • NAD
  • Niacinamide
  • Niacin
  • Phosphotransferases (Alcohol Group Acceptor)
  • nicotinamide riboside kinase
  • N-Glycosyl Hydrolases
  • Nicotinamidase