Haemin uptake and use as an iron source by Candida albicans: role of CaHMX1-encoded haem oxygenase.
Candida albicans, unlike Saccharomyces cerevisiae, was able to use extracellular haemin as an iron source. Haemin uptake kinetics by C. albicans cells showed two phases: a rapid phase of haemin binding (with a K(d) of about 0.2 microM) followed by a slower uptake phase. Both phases were strongly induced in iron-deficient cells compared to iron-rich cells. Haemin uptake did not depend on the previously characterized reductive iron uptake system and siderophore uptake system. CaHMX1, encoding a putative haem oxygenase, was shown to be required for iron assimilation from haemin. A double DeltaCahmx1 mutant was constructed. This mutant could not grow with haemin as the sole iron source, although haemin uptake was not affected. The three different iron uptake systems (reductive, siderophore and haemin) were regulated independently and in a complex manner. CaHMX1 expression was induced by iron deprivation, by haemin and by a shift of temperature from 30 to 37 degrees C. CaHMX1 expression was strongly deregulated in a Deltaefg1 mutant but not in a Deltatup1 mutant. C. albicans colonies forming on agar plates with haemin as the sole iron source showed a very unusual morphology. Colonies were made up of tubular structures that were organized into a complex network. The effect of haemin on filamentation was increased in the double DeltaCahmx1 mutant. This study provides the first experimental evidence that haem oxygenase is required for iron assimilation from haem by a pathogenic fungus.
Santos
Renata
R
Laboratoire d'Ingénierie des Protéines et Contrôle Métabolique, Institut Jacques Monod, Tour 43, Université Paris 6/Paris 7, 2 Place Jussieu, 75251 Paris cedex 05, France.
Buisson
Nicole
N
Laboratoire d'Ingénierie des Protéines et Contrôle Métabolique, Institut Jacques Monod, Tour 43, Université Paris 6/Paris 7, 2 Place Jussieu, 75251 Paris cedex 05, France.
Knight
Simon
S
University of Pennsylvania, Department of Medicine, Division of Hematology/Oncology, BRBII/III Room 731, 431 Curie Blvd, PA 19104, USA.
Dancis
Andrew
A
University of Pennsylvania, Department of Medicine, Division of Hematology/Oncology, BRBII/III Room 731, 431 Curie Blvd, PA 19104, USA.
Camadro
Jean-Michel
JM
Laboratoire d'Ingénierie des Protéines et Contrôle Métabolique, Institut Jacques Monod, Tour 43, Université Paris 6/Paris 7, 2 Place Jussieu, 75251 Paris cedex 05, France.
Lesuisse
Emmanuel
E
Laboratoire d'Ingénierie des Protéines et Contrôle Métabolique, Institut Jacques Monod, Tour 43, Université Paris 6/Paris 7, 2 Place Jussieu, 75251 Paris cedex 05, France.
D002176:Candida albicans / Q000235:genetics / Q000254:growth & development / Q000378:metabolism* / Q000472:pathogenicity; D003470:Culture Media; D015966:Gene Expression Regulation, Fungal; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism*; D006427:Hemin / Q000378:metabolism*; D006801:Humans; D007501:Iron / Q000378:metabolism*; D007700:Kinetics; D009154:Mutation; D014158:Transcription, Genetic
D003470:Culture Media; D006427:Hemin; D007501:Iron; D006419:Heme Oxygenase (Decyclizing)