A High-Affinity Iron Permease Essential for
            <i>Candida albicans</i>
            Virulence

Ramanan, Narendrakumar; Wang, Yan Ming

doi:10.1126/science.288.5468.1062

Cited by 297 publications

(379 citation statements)

References 21 publications

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“…Iron uptake has been shown to be important for virulence in C. albicans and it has been demonstrated that a homozygous Caftr1-null mutant is unable to establish a systemic infection in a mouse model (Ramanan & Wang, 2000). In S. cerevisiae, it has been observed that deletions in genes that facilitate high-affinity copper uptake or delivery of copper ions to the multicopper oxidase ScFet3p result in strains that also display defective high-affinity iron uptake (Knight et al, 1996;Lin et al, 1997;Yuan et al, 1995).…”

Section: Resultsmentioning

confidence: 99%

“…It has now been identified that this is also the case for the fungal pathogen Candida albicans (Ramanan & Wang, 2000). Iron acquisition presents a particular problem to pathogenic micro-organisms due to the hostile environment of the human host.…”

Section: Introductionmentioning

confidence: 99%

“…The CaFET3 gene encodes a multi-copper oxidase with the ability to rescue a S. cerevisiae fet3-null mutant (Eck et al, 1999) and CaFTR1 encodes an iron permease that is functionally homologous to ScFtr1p (Ramanan & Wang, 2000). C. albicans strains that carry deletions in CaFET3 or CaFTR1 display defects in reductive high-affinity iron uptake, and most notably a Caftr1-null mutant was unable to set up a systemic infection in mice (Eck et al, 1999;Ramanan & Wang, 2000). A siderophore uptake system has also been identified in C. albicans that is encoded by CaARN1 (Hu et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

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The CaCTR1 gene is required for high-affinity iron uptake and is transcriptionally controlled by a copper-sensing transactivator encoded by CaMAC1

Marvin

Cashmore

2004

Microbiology

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The ability of Candida albicans to acquire iron from the hostile environment of the host is known to be necessary for virulence and appears to be achieved using a similar system to that described for Saccharomyces cerevisiae. In S. cerevisiae, high-affinity iron uptake is dependent upon the acquisition of copper. The authors have previously identified a C. albicans gene (CaCTR1) that encodes a copper transporter. Deletion of this gene results in a mutant strain that grows predominantly as pseudohyphae and displays aberrant morphology in low-copper conditions. This paper demonstrates that invasive growth by C. albicans is induced by low-copper conditions and that this is augmented in a Cactr1-null strain. It also shows that deletion of CaCTR1 results in defective iron uptake. In S. cerevisiae, genes that facilitate high-affinity copper uptake are controlled by a copper-sensing transactivator, ScMac1p. The authors have now identified a C. albicans gene (CaMAC1) that encodes a copper-sensing transactivator. A Camac1-null mutant displays phenotypes similar to those of a Cactr1-null mutant and has no detectable CaCTR1 transcripts in low-copper conditions. It is proposed that high-affinity copper uptake by C. albicans is necessary for reductive iron uptake and is transcriptionally controlled by CaMac1p in a similar manner to that in S. cerevisiae.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The CaCTR1 gene is required for high-affinity iron uptake and is transcriptionally controlled by a copper-sensing transactivator encoded by CaMAC1

Marvin

Cashmore

2004

Microbiology

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“…Two genes, CFL1 (Hammacott et al, 2000) and RBT2 encode functional surface ferrireductases homologous to the S. cerevisiae Fre family. CaFET3, a multicopper oxidase gene involved in high-affinity ferrous transport, was recently cloned (Eck et al, 1999), and the high-affinity iron permease CaFTR1 was shown to be required for C. albicans virulence (Ramanan and Wang, 2000).…”

Section: Introductionmentioning

confidence: 99%

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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“…In addition, a system of low-affinity iron uptake seems to occur in P. brasiliensis, as inferred from the expression of ferric reductase and low-affinity iron transport permease ). In C. albicans there are two genes encoding iron permease and the high affinity transporter is required for virulence in a mouse model of infection (Ramanan & Wang 2000).…”

Section: The Most Prominent Metabolic Pathways Induced During the Dimmentioning

confidence: 99%

Preferential transcription of Paracoccidioides brasiliensis genes: host niche and time-dependent expression

Pereira

Bailão

Parente

et al. 2009

Mem. Inst. Oswaldo Cruz

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A High-Affinity Iron Permease Essential for Candida albicans Virulence

Cited by 297 publications

References 21 publications

The CaCTR1 gene is required for high-affinity iron uptake and is transcriptionally controlled by a copper-sensing transactivator encoded by CaMAC1

The CaCTR1 gene is required for high-affinity iron uptake and is transcriptionally controlled by a copper-sensing transactivator encoded by CaMAC1

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

Preferential transcription of Paracoccidioides brasiliensis genes: host niche and time-dependent expression

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