A multicopper oxidase gene from Candida albicans: cloning, characterization and disruption b bThe EMBL accession number for the sequence reported in this paper is Y09329.

Eck, Raimund; Hundt, Susanne Melanie; Härtl, Albert; Roemer, Ernst; Künkel, W.

doi:10.1099/00221287-145-9-2415

Cited by 98 publications

(75 citation statements)

References 29 publications

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“…Deletion of CaFET3 resulted in reduced adhesiveness to fibroblasts, although no significant differences were observed between the virulence of the wild type and the Δ/Δfet3 strain in a mouse model of systemic candidiasis [29]. In contrast with C. albicans , upon the removal of the ortholog of FET3 in C. parapsilosis indeed influenced the fungi’s virulence in vivo, given the lower amount of fungal burden measured.…”

Section: Discussionmentioning

confidence: 99%

Eicosanoid biosynthesis influences the virulence of Candida parapsilosis

et al. 2018

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Lipid mediators, derived from arachidonic acid metabolism, play an important role in immune regulation. The functions of bioactive eicosanoids range from modulating cytokine signaling and inflammasome formation to anti-inflammatory and pro-resolving activities. Human pathogenic fungi such as Candida albicans, Candida parapsilosis, Cryptococcus neoformans and Aspergillus fumigatus have been shown to produce such lipid mediators, associated with their virulence. To date, investigations into the molecular mechanisms of fungal eicosanoid biosynthesis in different species have revealed that several genes are associated with prostaglandin production. However, these routes remain uncharacterized in C. parapsilosis with early results suggesting it uses pathways distinct from those found in C. albicans. Therefore, we aimed to identify and characterize C. parapsilosis genes involved in eicosanoid biosynthesis. Following arachidonic acid treatment of C. parapsilosis cells, we identified several genes interfering with prostaglandin production. Out of the identified genes, homologues of a multi copper oxidase (FET3), an Acyl-CoA thiolase (POT1) and an Acyl-CoA oxidase (POX1-3) were found to play a significant role in prostaglandin synthesis. Furthermore, all three genes were confirmed to enhance C. parapsilosis pathogenicity, as the corresponding deletion mutants were cleared more efficiently by human macrophages and induced higher levels of pro-inflammatory cytokines. In addition, the mutants were less virulent than the wild-type strain in a mouse model of systemic infection. Taken together, we identified three genes that regulate eicosanoid biosynthesis in C. parapsilosis and impact the fungus’ virulence.

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Section: Discussionmentioning

confidence: 99%

Eicosanoid biosynthesis influences the virulence of Candida parapsilosis

et al. 2018

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“…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). Furthermore, growing evidence suggests that reductive iron uptake in C. albicans may also be dependent on copper uptake (Eck et al, 1999;Knight et al, 2002;Weissman et al, 2002).…”

Section: Resultsmentioning

confidence: 99%

“…A homozygous deletion of CaCCC2 results in strains with defective high-affinity iron uptake, presumably as a result of incorrect delivery and incorporation of copper into CaFet3p (Weissman et al, 2002). However, although reductive iron uptake has been shown to be reliant on copper in C. albicans, Cafet3 and Caccc2-null mutants were still able to set up a systemic infection in mice (Eck et al, 1999). Furthermore, the virulence of a Caarn1-null mutant was also unaffected (Hu et al, 2002).…”

Section: Introductionmentioning

confidence: 98%

“…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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“…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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A multicopper oxidase gene from Candida albicans: cloning, characterization and disruption b bThe EMBL accession number for the sequence reported in this paper is Y09329.

Cited by 98 publications

References 29 publications

Eicosanoid biosynthesis influences the virulence of Candida parapsilosis

Eicosanoid biosynthesis influences the virulence of Candida parapsilosis

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

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