HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 279, Issue 5, 3426-3433, January 30, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/5/3426    most recent M311550200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Pendrak, M. L. Articles by Roberts, D. D. Search for Related Content PubMed PubMed Citation Articles by Pendrak, M. L. Articles by Roberts, D. D. Social Bookmarking                      What's this?

Heme Oxygenase in Candida albicans Is Regulated by Hemoglobin and Is Necessary for Metabolism of Exogenous Heme and Hemoglobin to -Biliverdin^*

Michael L. Pendrak, Mark P. Chao, S. Steve Yan, and David D. Roberts¶

From the Laboratory of Pathology, NCI, National Institutes of Health, Bethesda, Maryland 20892-1500

Candida albicans is an opportunistic pathogen that has adapted uniquely to life in mammalian hosts. One of the host factors recognized by this yeast is hemoglobin, which binds to a specific cell surface receptor. In addition to its regulating the expression of adhesion receptors on the yeast, we have found that hemoglobin induces the expression of a C. albicans heme oxygenase (CaHmx1p). Hemoglobin transcriptionally induces the CaHMX1 gene independent of the presence of inorganic iron in the medium. A Renilla luciferase reporter driven by the CaHMX1 promoter demonstrated rapid activation of transcription by hemoglobin and (cobalt protoporphyrin IX) globin but not by apoglobin or other proteins. In contrast, iron deficiency or exogenous hemin did not activate the reporter until after 3 h, suggesting that induction of the promoter by hemoglobin is mediated by receptor signaling rather than heme or iron flux into the cell. As observed following disruption of the Saccharomyces cerevisiae ortholog, HMX1, a CaHMX1 null mutant was unable to grow under iron restriction. This suggests a role for CaHmx1p in inorganic iron acquisition. CaHMX1 encodes a functional heme oxygenase. Exogenous heme or hemoglobin is exclusively metabolized to -biliverdin. CaHMX1 is required for utilization of these exogenous substrates, indicating that C. albicans heme oxygenase confers a nutritional advantage for growth in mammalian hosts.

Received for publication, October 21, 2003 , and in revised form, November 10, 2003.

^* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Present address: Case Western Reserve University, Cleveland, OH 44106. E-mail: mxc107{at}po.cwru.edu.

Present address: FDA, 7500 Standish Place, HFV-150, Rockville, MD 20855. E-mail: syan{at}cvm.fda.gov.

^¶ To whom correspondence should be addressed: Laboratory of Pathology, Bldg. 10 Rm. 2A33, 10 Center Dr. MSC 1500, Bethesda, MD 20892. Tel.: 301-496-6264; Fax: 301-402-0043; E-mail: droberts{at}helix.nih.gov.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				Y.-U. Baek, M. Li, and D. A. Davis Candida albicans Ferric Reductases Are Differentially Regulated in Response to Distinct Forms of Iron Limitation by the Rim101 and CBF Transcription Factors Eukaryot. Cell, July 1, 2008; 7(7): 1168 - 1179. [Abstract] [Full Text] [PDF]

				O. Protchenko, M. Shakoury-Elizeh, P. Keane, J. Storey, R. Androphy, and C. C. Philpott Role of PUG1 in Inducible Porphyrin and Heme Transport in Saccharomyces cerevisiae Eukaryot. Cell, May 1, 2008; 7(5): 859 - 871. [Abstract] [Full Text] [PDF]

				R. T. Kinobe, R. A. Dercho, J. Z. Vlahakis, J. F. Brien, W. A. Szarek, and K. Nakatsu Inhibition of the Enzymatic Activity of Heme Oxygenases by Azole-Based Antifungal Drugs J. Pharmacol. Exp. Ther., October 1, 2006; 319(1): 277 - 284. [Abstract] [Full Text] [PDF]

				O. Protchenko, R. Rodriguez-Suarez, R. Androphy, H. Bussey, and C. C. Philpott A Screen for Genes of Heme Uptake Identifies the FLC Family Required for Import of FAD into the Endoplasmic Reticulum J. Biol. Chem., July 28, 2006; 281(30): 21445 - 21457. [Abstract] [Full Text] [PDF]

				S. A. B. Knight, G. Vilaire, E. Lesuisse, and A. Dancis Iron Acquisition from Transferrin by Candida albicans Depends on the Reductive Pathway Infect. Immun., September 1, 2005; 73(9): 5482 - 5492. [Abstract] [Full Text] [PDF]

				M. L. Pendrak, S. S. Yan, and D. D. Roberts Hemoglobin Regulates Expression of an Activator of Mating-Type Locus {alpha} Genes in Candida albicans Eukaryot. Cell, June 1, 2004; 3(3): 764 - 775. [Abstract] [Full Text] [PDF]