Nicotinic acid limitation regulates silencing of Candida adhesins during UTI.
The adherence of Candida glabrata to host cells is mediated, at least in part, by the EPA genes, a family of adhesins encoded at subtelomeric loci, where they are subject to transcriptional silencing. We show that normally silent EPA genes are expressed during murine urinary tract infection (UTI) and that the inducing signal is the limitation of nicotinic acid (NA), a precursor of nicotinamide adenine dinucleotide (NAD+). C. glabrata is an NA auxotroph, and NA-induced EPA expression is likely the result of a reduction in NAD+ availability for the NAD+-dependent histone deacetylase Sir2p. The adaptation of C. glabrata to the host, therefore, involves a loss of metabolic capacity and exploitation of the resulting auxotrophy to signal a particular host environment.
Domergue
Renee
R
Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Castaño
Irene
I
De Las Peñas
Alejandro
A
Zupancic
Margaret
M
Lockatell
Virginia
V
Hebel
J Richard
JR
Johnson
David
D
Cormack
Brendan P
BP
D000818:Animals; D041221:Candida glabrata / Q000235:genetics* / Q000254:growth & development / Q000472:pathogenicity* / Q000502:physiology; D002177:Candidiasis / Q000382:microbiology*; D002448:Cell Adhesion; D003470:Culture Media; D005260:Female; D015966:Gene Expression Regulation, Fungal; D020868:Gene Silencing; D005800:Genes, Fungal; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D037102:Lectins / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D009243:NAD / Q000378:metabolism; D009525:Niacin / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology / Q000652:urine; D009536:Niacinamide / Q000494:pharmacology / Q000652:urine; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D001743:Urinary Bladder / Q000382:microbiology; D014552:Urinary Tract Infections / Q000382:microbiology*; D014556:Urine / Q000382:microbiology; D019459:Urothelium / Q000382:microbiology; D014774:Virulence
D003470:Culture Media; D037102:Lectins; D009243:NAD; D009536:Niacinamide; D009525:Niacin; D037761:Sirtuins; D006655:Histone Deacetylases