Siderophore uptake and use by the yeast Saccharomyces cerevisiae

Abstract

The non-reductive uptake of several siderophores (ferrioxamine B, ferrichrome, triacetylfusarinine C and ferricrocin) by various strains of Saccharomyces cerevisiae was studied. Several aspects of siderophore transport were examined, including specificity of transport, regulation of transport and intracellular localization of the ferri-siderophores. Ferrioxamine B was taken up preferentially via the products of the SIT1 gene and triacetylfusarinine C by the TAF1 gene product, but the specificity was not absolute. Ferrichrome and ferricrocin uptake was not dependent on a single major facilitator superfamily (MFS) gene product. The apparent specificity of transport was strongly dependent on the genetic background of the cells. Non-reductive uptake of siderophores was induced under more stringent conditions (of iron deprivation) than was the reductive uptake of ferric citrate. Regulation of transport depended on the transcriptional factors Aft1 and Tup1/Ssn6. Cells disrupted for the TUP1 or SSN6 genes were constitutively derepressed for the uptake of ferrichrome, ferricrocin or ferrioxamine B, but not for the uptake of triacetylfusarinine C. Cells bearing the AFT1 up mutation accumulated large amounts of ferric siderophores. Intracellular decomplexation of the siderophores occurred when transcription of the AFT1 up gene was repressed. Ferrioxamine B and ferrichrome seemed to accumulate in an endosomal compartment, as shown by biochemical studies and by confocal microscopy study of cells loaded with a fluorescent derivative of ferrichrome. Endocytosis was, however, not involved in the non-reductive uptake of siderophores.

Siderophore uptake by Candida albicans: effect of serum treatment and comparison with Saccharomyces cerevisiae

“…Closed circles, ferrichrome; open circles, ferricrocin; closed squares, triacethylfusarinine C; open squares, ferrioxamine B 332 E. Lesuisse et al observed in S. cerevisiae (Lesuisse et al, 2001). In that organism also, TAF was taken up at a much lower rate than FCH and FC, although a specific high-affinity mechanism for TAF transport was noted (Heymann et al, 1999;Lesuisse et al, 2001). Further evidence for cellular uptake of siderophores by Candida albicans was obtained by examining uptake of a fluorescent analogue of ferrichrome 12G.…”

“…The cells were suspended at about 1 mg protein/ml in 50 mM citrate buffer (pH 6.5) containing 5% glucose and incubated at 30uC with 1 mM of various 55 Fe-siderophores. Closed circles, ferrichrome; open circles, ferricrocin; closed squares, triacethylfusarinine C; open squares, ferrioxamine B 332 E. Lesuisse et al observed in S. cerevisiae (Lesuisse et al, 2001). In that organism also, TAF was taken up at a much lower rate than FCH and FC, although a specific high-affinity mechanism for TAF transport was noted (Heymann et al, 1999;Lesuisse et al, 2001).…”

“…In this way, S. cerevisiae can transport siderophores excreted by other microorganisms, although it does not produce any itself. Non-reductive siderophore transport systems in this yeast have been described for ferrioxamine B (mesylate form) (FOB) (Lesuisse and Labbe, 1989;Lesuisse et al, 1998), ferrichrome (FCH) (Yun et al, 2000), triacetylfusarinine C (TAF) (Heymann et al, 1999), enterobactin (ENB) (Heymann et al, 2000a) and ferricrocin (FC) (Heymann et al, 2000b;Lesuisse et al, 2001). The gene products involved (Sit1p, Arn1p, Taf1p and Enb1p) belong to the major facilitator superfamily (MFS).…”

“…The genes involved in both reductive and non-reductive uptake of iron by S. cerevisiae are transcriptionally regulated via the activator Aft1 (Yamaguchi-Iwai et al, 1995;Yun et al, 2000). In addition, the Tup1/Ssn6 repressor regulates transcription of the genes involved in non-reductive transport of siderophores (Lesuisse et al, 2001).…”

Identification of the molecular mechanisms underlying the cytotoxic action of a potent platinum metallointercalator

“…The transport pathway was represented by 17 genes including FTR1, ARN1, ARN2, SIT1 (ARN3), ENB1 (ARN4), FRE1, FRE2, FRE3, FRE6, FIT2, FIT3, CTR1, CCC2, SIT1, PUG1, VMR1, DTR1 and RSB1. All of these genes except four (PUG1, VMR1, DTR1 and RSB1) are in the pathway of iron and copper transport across the cell membrane [24,30,49,57]. For example, FTR1 gene encodes a high-affinity iron permease for the transport of iron across the plasma membrane [69] and ARN1 encodes a membrane transporter responsible for up-taking iron bounded to siderophores [30].…”