Nicotinic Acid Limitation Regulates Silencing of Candida Adhesins During UTI
Abstract
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.
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EPA6 is expressed in the murine urinary tract infection model due to unavailability of nicotinic acid, a precursor for the CgSir2 histone deacetylase cofactor NAD+.
“Furthermore, EPA6 was found to be expressed in the murine urinary tract infection model, due to unavailability of the nicotinic acid, which is a precursor for the CgSir2 histone deacetylase cofactor, nicotinamide adenine dinucleotide (NAD+) [30].”
From Candida glabrata: A Lot More Than Meets the Eye (2019) · cites this paper as [30]
Epa6 and Epa7 adhesins mediate adherence to epithelial and endothelial cells.
“The Epa6 and Epa7 adhesins have been shown to mediate adherence to epithelial and endothelial cells [30,35].”
From Candida glabrata: A Lot More Than Meets the Eye (2019) · cites this paper as [30]
The majority of Epa adhesins are encoded by sub-telomeric localized genes and regulated by epigenetic SIR-dependent transcriptional silencing.
“The majority of Epa adhesins are encoded by sub-telomeric localized genes and regulated by epigenetic SIR (Silent Information Regulator)-dependent transcriptional silencing [27,29,30,31].”
From Candida glabrata: A Lot More Than Meets the Eye (2019) · cites this paper as [30]
Epa6 and Epa7 are pivotal to adherence under specific environmental conditions.
“Although the in vitro adherence of C. glabrata to epithelial cells is primarily mediated by the Epa1 adhesin [32], Epa6 and Epa7 have been shown to be pivotal to adherence under specific environmental conditions [30,36].”
From Candida glabrata: A Lot More Than Meets the Eye (2019) · cites this paper as [30]
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References 25 · Cited by 249
- Authors
- Domergue, R., Castaño, I., De Las Peñas, A., Zupancic, M., Lockatell, V., Hebel, J. R., Johnson, D., & Cormack, B. P.
- Affiliations
- University of Maryland, Baltimore (US)
- Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
- Corresponding author
- Cormack, Brendan P.
- ORCID
- Cormack, Brendan P.
- Venue
- Science
- Published
- 2005-05-06
- Volume
- 308
- Issue
- 5723
- Pages
- 866-870
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2078752695
- Cited by
- 249
- References
- 25
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 8 · 2023: 3 · 2022: 11 · 2021: 8 · 2020: 13 · 2019: 9 · 2018: 17 · 2017: 6 · 2016: 18 · 2015: 13 · 2014: 18 · 2013: 21 · 2012: 14
- FWCI
- 4.24
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (R01AI046223)
- National Institute of Diabetes and Digestive and Kidney Diseases (2PO1 DK49720, P01DK049720)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
- Keywords
- Candida glabrata, nicotinic acid, NAD+, Sir2p, histone deacetylase, transcriptional silencing, urinary tract infection, host-pathogen interaction, auxotrophy, fungal adhesion
- MeSH terms
- Animals, Urinary Bladder, Candidiasis, Cell Adhesion, Culture Media, Female, Genes, Fungal, Histone Deacetylases, Mice, Inbred BALB C, Mice, Inbred CBA, NAD, Niacin, Niacinamide, Transcription, Genetic, Urinary Tract Infections, Urine, Virulence, Gene Expression Regulation, Fungal, Urothelium, Gene Silencing, Lectins, Sirtuins, Candida glabrata, Mice
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