Assimilation of NAD(+) precursors in Candida glabrata.
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.
Ma
Biao
B
Department of Molecular Biology and Genetics, Johns Hopkins School of Medicine, Hunterian 617, 725 North Wolfe Street, Baltimore, MD 21205-2185, USA.
Pan
Shih-Jung
SJ
Zupancic
Margaret L
ML
Cormack
Brendan P
BP
D000818:Animals; D041221:Candida glabrata / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D017353:Gene Deletion; D053858:Metabolic Networks and Pathways; D051379:Mice; D009699:N-Glycosyl Hydrolases / Q000235:genetics / Q000378:metabolism; D009243:NAD / Q000096:biosynthesis*; D009525:Niacin / Q000378:metabolism; D009536:Niacinamide / Q000031:analogs & derivatives / Q000378:metabolism; D009535:Nicotinamidase / Q000235:genetics / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism; D011726:Pyridinium Compounds
D011726:Pyridinium Compounds; C018613:nicotinamide-beta-riboside; D009243:NAD; D009536:Niacinamide; D009525:Niacin; D017853:Phosphotransferases (Alcohol Group Acceptor); C061783:nicotinamide riboside kinase; D009699:N-Glycosyl Hydrolases; D009535:Nicotinamidase