Effect of iron deprivation on surface composition and virulence determinants of Candida albicans

Sweet, S. P.; Douglas, L. Julia

doi:10.1099/00221287-137-4-859

Cited by 23 publications

(26 citation statements)

References 22 publications

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“…Lan et al (18) reported that genes related to the TCA pathway were more highly expressed under the highiron condition; accordingly, our results would point to conditions with limited iron availability. Furthermore, iron depletion is known to alter the cell surface composition and hydrophobicity of C. albicans (31,41,42), and we found four genes encoding GPI-anchored proteins to be upregulated in response to MAb C7. In particular was RBT5, a protein from a family of pathogenesis-related heme-binding proteins (44) which is highly upregulated under low-iron conditions (16).…”

Section: Discussionmentioning

confidence: 88%

Fungicidal Monoclonal Antibody C7 Interferes with Iron Acquisition in Candida albicans

Brena

Cabezas-Olcoz

Moragues

et al. 2011

Antimicrob Agents Chemother

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We have developed a monoclonal antibody (MAb), C7, that reacts with the Als3p and enolase present in the Candida albicans cell wall and exerts three anti-Candida activities: candidacidal activity and inhibition of both adhesion and filamentation. To investigate the mode of action of MAb C7 on fungal viability, we examined changes in the genome-wide gene expression profile of C. albicans grown in the presence of a subinhibitory concentration of MAb C7 (12.5 g/ml) by using microarrays. A total of 49 genes were found to be differentially expressed upon treatment with MAb C7. Of these, 28 were found to be upregulated and 21 were found to be downregulated. The categories of upregulated genes with the largest number of variations were those involved in iron uptake or related to iron homeostasis (42.86%), while the energy-related group accounted for 38.10% of the downregulated genes (8/21). Results were validated by real-time PCR. Since these effects resembled those found under iron-limited conditions, the activity of MAb C7 on C. albicans mutants with deletions in key genes implicated in the three iron acquisition systems described in this yeast was also assessed. Only mutants lacking the TPK1 gene and, to a lesser extent, the TPK2 gene were less sensitive to the candidacidal effect of MAb C7. FeCl 3 or hemin at concentrations of >7.8 M reversed the candidacidal effect of MAb C7 on C. albicans in a concentration-dependent manner. The results presented in this study provide evidence that the candidacidal effect of MAb C7 is related to the blockage of the reductive iron uptake pathway of C. albicans.

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Section: Discussionmentioning

confidence: 88%

Fungicidal Monoclonal Antibody C7 Interferes with Iron Acquisition in Candida albicans

Brena

Cabezas-Olcoz

Moragues

et al. 2011

Antimicrob Agents Chemother

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“…The production of pseudohyphae by strain BWP17ctr1D : : URA3/ctr1D : : ARG4 in low-copper medium may result from the cell responding to copper-starved conditions. However, it has previously been observed that low-iron conditions affect hyphal growth in C. albicans (Sweet & Douglas, 1991) and so the lack of copper transport affecting iron uptake due to inactive CaFet3p activity may also be a contributing factor.…”

Section: Discussionmentioning

confidence: 99%

“…The presence of CuRE-like elements in the promoter of CaCTR1 may facilitate tight control of copper uptake by a Mac1p-like transactivator, leading to copper homeostasis. Iron availability has been shown to affect C. albicans growth, hyphal production, adherence to host cells and the ability to set up an infection in mice (Sweet & Douglas, 1991;Valenti et al, 1986;Moors et al, 1992;Fratti et al, 1998;Eck et al, 1999;Ramanan & Wang, 2000). In S. cerevisiae the dependence of iron acquisiton on the uptake and delivery of copper to Fet3p is well documented and evidence suggests that a similar system operates in C. albicans (Morrissey et al, 1996;Eck et al, 1999;Hamacott et al, 2000;Ramanan & Wang, 2000).…”

Section: Discussionmentioning

confidence: 99%

“…The organism can acquire iron from haem and can bind to and lyse erythrocytes (Manns et al, 1994;Moors et al, 1992). Although C. albicans can produce siderophores (Ismail et al, 1985;Sweet & Douglas, 1991) it is still not clear how it obtains ferrous iron from these complexes or from other sources. Growing evidence suggests that a similar reductive system to that described for S. cerevisiae operates in C. albicans and several homologous genes have been identified.…”

Section: Introductionmentioning

confidence: 99%

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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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“…As with other microbial pathogens, virulence of C. albicans is likely to be multifactorial ; characteristics such as proteinase secretion, adherence to host cells and hyphal production have all been implicated in virulence (Hube et al, 1997 ;Gale et al, 1998). Moreover, hyphal production and adherence have both been shown to be altered by growth in low-iron conditions (Sweet & Douglas, 1991a). It is probable, therefore, that iron acquisition plays a key role in the pathogenesis of C. albicans disease in ways similar to those proposed for many The EMBL accession number for the sequence reported in this paper is AJ387722.…”

Section: Introductionmentioning

confidence: 99%

Candida albicans CFL1 encodes a functional ferric reductase activity that can rescue a Saccharomyces cerevisiae fre1 mutant The EMBL accession number for the sequence reported in this paper is AJ387722.

2000

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Candida albicans, like other pathogens, has to compete with the host for a limited supply of available iron. Consequently, iron acquisition is likely to be an important factor for the growth, survival and virulence of this organism. It was previously demonstrated that C. albicans has a surface-associated ferric reductase similar to that of Saccharomyces cerevisiae. Therefore, functional rescue of a S. cerevisiae fre1 mutant was used to isolate a C. albicans ferric reductase gene (CFL1). This gene has been previously identified. However, the workers had not observed any functional reductase activity associated with the gene. The discrepancy with the findings in this report appears to be due to the clone previously reported carrying a non-contiguous piece of C. albicans DNA. Results shown in this paper demonstrate that CFL1 transcription is regulated in response to levels of iron and copper. This is the first demonstration of a functional ferric reductase gene from C. albicans.

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Effect of iron deprivation on surface composition and virulence determinants of Candida albicans

Cited by 23 publications

References 22 publications

Fungicidal Monoclonal Antibody C7 Interferes with Iron Acquisition in Candida albicans

Fungicidal Monoclonal Antibody C7 Interferes with Iron Acquisition in Candida albicans

The Candida albicans CTR1 gene encodes a functional copper transporter

Candida albicans CFL1 encodes a functional ferric reductase activity that can rescue a Saccharomyces cerevisiae fre1 mutant The EMBL accession number for the sequence reported in this paper is AJ387722.

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