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Science 308 (5723): 866-870

Copyright © 2005 by the American Association for the Advancement of Science

Nicotinic Acid Limitation Regulates Silencing of Candida Adhesins During UTI

Renee Domergue,1 Irene Castaño,1* Alejandro De Las Peñas,1* Margaret Zupancic,1 Virginia Lockatell,2 J. Richard Hebel,3 David Johnson,2,4 Brendan P. Cormack1{dagger}

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.

1 Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
2 Division of Infectious Diseases, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
3 Department of Epidemiology and Preventive Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
4 Research Service, Department of Veterans Affairs, Baltimore, MD 21201, USA.

Published online 17 March 2005;

Include this information when citing this paper.

* Present address: Instituto Potosino de Investigacion Cientifica y Tecnologica, Division de Biologia Molecular, Camino a la Presa San Jose 2055, 78216 San Luis Potosi, San Luis Potosi, Mexico.

{dagger} To whom correspondence should be addressed. E-mail: bcormack{at}jhmi.edu

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