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Published Online March 17, 2005
Science DOI: 10.1126/science.1108640

Reports

Submitted on December 13, 2004
Accepted on February 23, 2005

Nicotinic Acid Limitation Regulates Silencing of Candida Adhesins During UTI

Renee Domergue 1, Irene Castaño 2, Alejandro De Las Peñas 2, Margaret Zupancic 1, Virginia Lockatell 3, Richard J. Hebel 4, David Johnson 5, Brendan P. Cormack 1*

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

* To whom correspondence should be addressed.
Brendan P. Cormack , E-mail: bcormack{at}jhmi.edu

Adherence of Candida glabrata to host cells is mediated, at least in part, by the EPA genes, a family of adhesins encoded at sub-telomeric 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 limitation for nicotinic acid (NA), a precursor of NAD+. C. glabrata is a 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 loss of metabolic capacity and exploitation of the resulting auxotrophy to signal a particular host environment.


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