Identification and substrate specificity of a ferrichrome-type siderophore transporter (Arn1p) in Saccharomyces cerevisiae

Heymann, Petra; Ernst, Joachim F.; Winkelmann, G.

doi:10.1111/j.1574-6968.2000.tb09108.x

Cited by 106 publications

(87 citation statements)

References 22 publications

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“…Values from two independent experiments Siderophore uptake by Candida albicans 333 up and visualized within cells. This information, together with evidence of saturable high-affinity transport suggests the existence of specific mechanisms for the uptake of siderophores by C. albicans, as previously shown for S. cerevisiae (Lesuisse et al, 1998(Lesuisse et al, , 2001Heymann et al, 2000aHeymann et al, , 2000bYun et al, 2000).…”

Section: High-affinity Uptake Of Siderophores By C Albicanssupporting

confidence: 77%

“…In S. cerevisiae, homologous genes of the major facilitator superfamily (SIT1, TAF1, ENB1, ARN1) are directly involved in siderophore transport (Lesuisse et al, 1998(Lesuisse et al, , 2001Heymann et al, 2000aHeymann et al, , 2000bYun et al, 2000). A gene homologous to this gene family, CaSIT1, was found in C. albicans by searching the databases.…”

Section: Iron Deprivation During Growth Induces Iron Uptake From Sidementioning

confidence: 99%

“…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).…”

Section: Introductionmentioning

confidence: 99%

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

Lesuisse

Knight

Camadro

et al. 2002

Yeast

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Iron uptake systems often function as virulence factors in pathogenic organisms. Candida albicans is a fungal pathogen that infects immunocompromised hosts, such as AIDS patients or granulocytopenic bone marrow transplant recipients. Here we show that iron uptake from siderophores occurs in C. albicans and is mediated by one or more highaffinity transport systems. Iron carried on ferrioxamine B, triacethyl-fusarinine, ferrichrome, or ferricrocin was actively taken up via a high-affinity mechanism. The kinetic parameters of uptake were similar to those found in S. cerevisiae. Furthermore, for ferrichrome and ferrioxamine B, cellular uptake of fluorescent analogues was observed. In C. albicans, iron uptake from siderophores was regulated by iron availability, with iron deprivation inducing uptake. Serum exposure, which induces a morphogenic shift from yeast to filamentous forms known to be required for virulence, also resulted in induction of iron transport from ferrichrome-type siderophores. In a tup1/tup1 strain which grows constitutively in the filamentous form, iron transport was derepressed for all siderophores tested. The genes mediating uptake and utilization of iron from siderophores in C. albicans have not been identified; however, the transcript abundance for CaSIT1 was regulated in a manner consistent with the pattern of iron uptake from ferrichrome-type siderophores. Furthermore, CaSIT1 overexpression in S. cerevisiae resulted in inhibited siderophore iron uptake, suggesting that the expressed protein may interact with proteins of S. cerevisiae involved in iron uptake from siderophores. In summary, iron uptake from ferrichrome-type siderophores was induced in filamentous C. albicans, and a potential role of this iron acquisition system in pathogenicity should be considered.

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Section: High-affinity Uptake Of Siderophores By C Albicanssupporting

confidence: 77%

Section: Iron Deprivation During Growth Induces Iron Uptake From Sidementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Lesuisse

Knight

Camadro

et al. 2002

Yeast

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“…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]. The cellular homeostasis pathway was represented by FTR1, ARN1, ARN2, SIT1 (ARN3), FRE3, FRE6, CCC2, TIS11, HMX1 and ENB1 (total of ten genes).…”

Section: Cytotoxicity Of 56mess In the Cisplatin-resistant L1210cisr mentioning

confidence: 99%

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

et al. 2011

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Platinum-based DNA metallointercalators are structurally different from the covalent DNA binders such as cisplatin and its derivatives but have potent in vitro activity in cancer cell lines. However, limited understanding of their molecular mechanisms of cytotoxic action greatly hinders their further development as anticancer agents. In this study, a lead platinum-based metallointercalator, [(5,6-dimethyl-1,10-phenanthroline) (1S,2S-diaminocyclohexane) platinum(II)] 2+ (56MESS) was found to be 163-fold more active than cisplatin in a cisplatin-resistant cancer cell line. By using transcriptomics in a eukaryotic model organism, yeast Saccharomyces cerevisiae, we identified 93 genes that changed their expressions significantly upon exposure of 56MESS in comparison to untreated controls (p≤0.05). Bioinformatic analysis of these genes demonstrated that iron and copper metabolism, sulfur-containing amino acids and stress response were involved in the cytotoxicity of 56MESS. Follow-up experiments showed that the iron and copper concentrations were much lower in 56MESS-treated cells compared to controls as measured by inductively coupled plasma optical emission spectrometry. Deletion mutants of the key genes in the iron and copper metabolism pathway and glutathione synthesis were sensitive to 56MESS. Taken together, the study demonstrated that the cytotoxic action of 56MESS is mediated by its ability to disrupt iron and copper metabolism, suppress the biosynthesis of sulfur-containing amino acids and attenuate cellular defence capacity. As these mechanisms are in clear contrast to the DNA binding mechanism for cisplatin and its derivative, 56MESS may be able to overcome cisplatinresistant cancers. These findings have provided basis to further develop the platinum-based metallointercalators as anticancer agents.

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“…The copper-responsive activator Mac1p regulates FRE1, CTR1, CTR3 and FRE7, the uncharacterized homologue of FRE1, while the iron-responsive activator Aft1p regulates FRE1, FRE2, FRE3-6, FTR1, FET3, ATX1, CCC2, and a family of intracellular siderophore transporter genes ARN1-4 (Dancis et al, 1992;Lin et al, 1997;Jungmann et al, 1993;Yamaguchi-Iwai et al, 1996;Labbe et al, 1997;Martins et al, 1998;Lesuisse et al, 1998;Heymann et al, 2000;Yun et al, 2000a, b). Thus FRE1 is regulated by both copper and iron through the activity of Mac1p and Aft1p, whereas the copper-trafficking genes ATX1 and CCC2 are regulated by iron through the activity of Aft1p.…”

Section: Introductionmentioning

confidence: 99%

The Candida albicans CTR1 gene encodes a functional copper transporter

2003

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Copper and iron uptake in Saccharomyces cerevisiae are linked through a high-affinity ferric/cupric-reductive uptake system. Evidence suggests that a similar system operates in Candida albicans. The authors have identified a C. albicans gene that is able to rescue a S. cerevisiae ctr1/ctr3-null mutant defective in high-affinity copper uptake. The 756 bp ORF, designated CaCTR1, encodes a 251 amino acid protein with a molecular mass of 27·8 kDa. Comparisons between the deduced amino acid sequence of the C. albicans Ctr1p and S. cerevisiae Ctr1p indicated that they share 39·6 % similarity and 33·0 % identity over their entire length. Within the predicted protein product of CaCTR1 there are putative transmembrane regions and sequences that resemble copper-binding motifs. The promoter region of CaCTR1 contains four sequences with significant identity to S. cerevisiae copper response elements. CaCTR1 is transcriptionally regulated in S. cerevisiae in response to copper availability by the copper-sensing transactivator Mac1p. Transcription of CaCTR1 in C. albicans is also regulated in a copper-responsive manner. This raises the possibility that CaCTR1 may be regulated in C. albicans by a Mac1p-like transactivator. A C. albicans ctr1-null mutant displays phenotypes consistent with the lack of copper uptake including growth defects in low-copper and low-iron conditions, a respiratory deficiency and sensitivity to oxidative stress. Furthermore, changes in morphology were observed in the C. albicans ctr1-null mutant. It is proposed that CaCTR1 facilitates transport of copper into the cell.

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Identification and substrate specificity of a ferrichrome-type siderophore transporter (Arn1p) in Saccharomyces cerevisiae

Cited by 106 publications

References 22 publications

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

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

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

The Candida albicans CTR1 gene encodes a functional copper transporter

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