title: Iron acquisition from transferrin by Candida albicans depends on the reductive pathway.
abstract: Host-pathogen interactions that alter virulence are influenced by critical nutrients such as iron. In humans, free iron is unavailable, being present only in high-affinity iron binding proteins such as transferrin. The fungal pathogen Candida albicans grows as a saprophyte on mucosal surfaces. Occasionally it invades systemically, and in this circumstance it will encounter transferrin iron. Here we report that C. albicans is able to acquire iron from transferrin. Iron-loaded transferrin restored growth to cultures arrested by iron deprivation, whereas apotransferrin was unable to promote growth. By using congenic strains, we have been able to show that iron uptake by C. albicans from transferrin was mediated by the reductive pathway (via FTR1). The genetically separate siderophore and heme uptake systems were not involved. FRE10 was required for a surface reductase activity and for efficient transferrin iron uptake activity in unbuffered medium. Other reductase genes were apparently up-regulated in medium buffered at pH 6.3 to 6.4, and the fre10(-/-) mutant had no effect under these conditions. Experiments in which transferrin was sequestered in a dialysis bag demonstrated that cell contact with the substrate was required for iron reduction and release. The requirement of FTR1 for virulence in a systemic infection model and its role in transferrin iron uptake raise the possibility that transferrin is a source of iron during systemic C. albicans infections.
authors.affiliation: University of Pennsylvania, Department of Medicine, Division of Hematology/Oncology, 731 BRB II/III, 421 Curie Blvd., Philadelphia, PA 19104-6160, USA. sknight@mail.med.upenn.edu
authors.forename: Simon A B
authors.initials: SA
authors.lastname: Knight
authors.forename: Gaston
authors.initials: G
authors.lastname: Vilaire
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Lesuisse
authors.forename: Andrew
authors.initials: A
authors.lastname: Dancis
mesh_terms: D001059:Apoproteins / Q000378:metabolism; D002176:Candida albicans / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D003300:Copper / Q000378:metabolism; D005291:Ferrichrome / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D007501:Iron / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D010084:Oxidation-Reduction; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D014168:Transferrin / Q000378:metabolism*
chemical_list: D001059:Apoproteins; C429223:FTR1 protein, Candida albicans; D005656:Fungal Proteins; D026901:Membrane Transport Proteins; D014168:Transferrin; C028284:apotransferrin; C110714:holotransferrin; D005291:Ferrichrome; D003300:Copper; D007501:Iron