Genome-wide expression profiling of the response to ciclopirox olamine in Candida albicans

Lee, Robin E. B.; Liu, Teresa T.; Barker, Katherine S.; Lee, Richard; Rogers, P. David

doi:10.1093/jac/dki105

Cited by 51 publications

(32 citation statements)

References 33 publications

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“…This response is sim- ilar to that registered for C. albicans treated with ciclopirox olamine, an antifungal drug that acts as an iron chelator, restricting the iron availability to the fungal cell and consequently inhibiting growth (19,28). In our hands, the presence of the chelator ferrozine reduced the C. albicans growth extent in a manner similar to that caused by MAb C7.…”

Section: Discussionsupporting

confidence: 76%

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: Discussionsupporting

confidence: 76%

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 also note that a previous study reported upregulation of FRE7 in C. neoformans under low-copper conditions (43). Besides metal regulation, transcription of ferric reductase genes in fungal pathogens is also affected by pH, macrophage engulfment, antifungal drugs, and infection, suggesting distinct regulation of different ferric reductases in response to specific environmental conditions (23,(44)(45)(46). These factors remain to be examined in C. neoformans, and more detailed interpretation of expression patterns and reductase activities will also require knowledge of the localization of each enzyme.…”

Section: Discussionmentioning

confidence: 62%

Role of Ferric Reductases in Iron Acquisition and Virulence in the Fungal Pathogen Cryptococcus neoformans

Saikia

Oliveira

et al. 2014

Infect Immun

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Iron acquisition is critical for the ability of the pathogenic yeast Cryptococcus neoformans to cause disease in vertebrate hosts. In particular, iron overload exacerbates cryptococcal disease in an animal model, defects in iron acquisition attenuate virulence, and iron availability influences the expression of major virulence factors. C. neoformans acquires iron by multiple mechanisms, including a ferroxidase-permease high-affinity system, siderophore uptake, and utilization of both heme and transferrin. In this study, we examined the expression of eight candidate ferric reductase genes and their contributions to iron acquisition as well as to ferric and cupric reductase activities. We found that loss of the FRE4 gene resulted in a defect in production of the virulence factor melanin and increased susceptibility to azole antifungal drugs. In addition, the FRE2 gene was important for growth on the iron sources heme and transferrin, which are relevant for proliferation in the host. Fre2 may participate with the ferroxidase Cfo1 of the high-affinity uptake system for growth on heme, because a mutant lacking both genes showed a more pronounced growth defect than the fre2 single mutant. A role for Fre2 in iron acquisition is consistent with the attenuation of virulence observed for the fre2 mutant. This mutant also was defective in accumulation in the brains of infected mice, a phenotype previously observed for mutants with defects in high-affinity iron uptake (e.g., the cfo1 mutant). Overall, this study provides a more detailed view of the iron acquisition components required for C. neoformans to cause cryptococcosis.

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“…Proteomic analysis of cytoplasmic proteins also showed upregulation between sensitive and resistant strains [26]. Expression of ORF19.822 is upregulated in transcription profiling studies in the presence of the drug ciclopirox olamine [27] and in the absence of adenylate cyclase (CYR1) [28] but down regulated when grown on bovine serum albumin in the presence of subinhibitory fluconazole [29]. This appears to be the first verification of this hypothetical protein.…”

Section: Discussionmentioning

confidence: 90%

Non-glucan Attached Proteins of Candida albicans Biofilm Formed on Various Surfaces

Vediyappan

Chaffin

2006

Mycopathologia

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Non-glucan attached proteins of the cell surface and extracellular matrix of Candida albicans biofilms formed on two catheter surfaces and denture acrylic were examined. The SDS-PAGE protein profiles of these proteins compared with that obtained from planktonic yeast cells and germ tubes were generally similar. This observation suggested that this class of biofilm surface proteins is not composed of a unique set of extracellular proteins or that one or a few proteins dominate the non-glucan attached proteins of biofilm. However, differences were observed in the proteins obtained from biofilm formed on one catheter surface and two proteins, Grp2p and ORF19.822p, identified by mass spectrometry following two-dimensional separation. These proteins have previously been associated with drug resistance and their presence or abundance appeared to be influenced by the surface on which the biofilm was formed.

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Genome-wide expression profiling of the response to ciclopirox olamine in Candida albicans

Cited by 51 publications

References 33 publications

Fungicidal Monoclonal Antibody C7 Interferes with Iron Acquisition in Candida albicans

Fungicidal Monoclonal Antibody C7 Interferes with Iron Acquisition in Candida albicans

Role of Ferric Reductases in Iron Acquisition and Virulence in the Fungal Pathogen Cryptococcus neoformans

Non-glucan Attached Proteins of Candida albicans Biofilm Formed on Various Surfaces

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