High-affinity transporters for NAD+ precursors in Candida glabrata are regulated by Hst1 and induced in response to niacin limitation

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DOIResolve DOI: http://doi.org/10.1128/MCB.01461-08
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TypeArticle
Journal titleMolecular and cellular biology
Volume29
Issue15
Pages40674079; # of pages: 13
AbstractThe yeast Candida glabrata is an opportunistic pathogen of humans. C. glabrata is a NAD+ auxotroph, and its growth depends on the availability of niacin (environmental vitamin precursors of NAD+). We have previously shown that a virulence-associated adhesin, encoded by EPA6, is transcriptionally induced in response to niacin limitation. Here we used transcript profiling to characterize the transcriptional response to niacin limitation and the roles of the sirtuins Hst1, Hst2, and Sir2 in mediating this response. The majority of genes transcriptionally induced by niacin limitation are regulated by Hst1, suggesting that it is the primary sensor of niacin limitation in C. glabrata. We show that three highly induced genes, TNA1, TNR1, and TNR2, encode transporters which are necessary and sufficient for high-affinity uptake of NAD+ precursors. Strikingly, if a tna1 tnr1 tnr2 mutant is starved for niacin, it exhibits an extended lag phase, suggesting a central role for the transporters in restoring NAD+ homeostasis after niacin limitation. Lastly, we had previously shown that the adhesin encoded by EPA6 is induced during experimental urinary tract infection (UTI); we show here that EPA6 transcriptional induction during UTI is strongly enhanced in the tna1 tnr1 tnr2 mutant strain, implicating the transporters in the growth of C. glabrata during infection.
Publication date
LanguageEnglish
AffiliationNational Research Council Canada (NRC-CNRC); NRC Biotechnology Research Institute
Peer reviewedYes
NRC number50666
NPARC number16499151
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Record identifier318f71b7-36ee-46a9-b315-19ceb0d8d862
Record created2010-12-06
Record modified2016-05-09
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