scholarly journals Effect of biogenic selenium nanoparticles on ERG11 and CDR1 gene expression in both fluconazole-resistant and -susceptible Candida albicans isolates

2017 ◽  
Vol 3 (3) ◽  
pp. 16-20 ◽  
Author(s):  
Nasrin Parsamehr ◽  
Sasan Rezaie ◽  
Sadegh Khodavaisy ◽  
Samira Salari ◽  
Sanaz Hadizadeh ◽  
...  
Keyword(s):  
Gene Expression ◽  
Candida Albicans ◽  
Selenium Nanoparticles ◽  
Fluconazole Resistant ◽  
Biogenic Selenium Nanoparticles

scholarly journals Competitive Fitness of Fluconazole-Resistant Clinical Candida albicans Strains

2017 ◽  
Vol 61 (7) ◽  
Author(s):  
Christina Popp ◽  
Irene A. I. Hampe ◽  
Tobias Hertlein ◽  
Knut Ohlsen ◽  
P. David Rogers ◽  
...  
Keyword(s):  
Gene Expression ◽  
Drug Resistance ◽  
Candida Albicans ◽  
Transcription Factors ◽  
Mouse Model ◽  
Ergosterol Biosynthesis ◽  
Fitness Costs ◽  
Content Type ◽  
Constitutive Overexpression ◽  
Fluconazole Resistant

ABSTRACT The pathogenic yeast Candida albicans can develop resistance to the widely used antifungal agent fluconazole, which inhibits ergosterol biosynthesis. Resistance is often caused by gain-of-function mutations in the transcription factors Mrr1 and Tac1, which result in constitutive overexpression of multidrug efflux pumps, and Upc2, which result in constitutive overexpression of ergosterol biosynthesis genes. However, the deregulated gene expression that is caused by hyperactive forms of these transcription factors also reduces the fitness of the cells in the absence of the drug. To investigate whether fluconazole-resistant clinical C. albicans isolates have overcome the fitness costs of drug resistance, we assessed the relative fitness of C. albicans isolates containing resistance mutations in these transcription factors in competition with matched drug-susceptible isolates from the same patients. Most of the fluconazole-resistant isolates were outcompeted by the corresponding drug-susceptible isolates when grown in rich medium without fluconazole. On the other hand, some resistant isolates with gain-of-function mutations in MRR1 did not exhibit reduced fitness under these conditions. In a mouse model of disseminated candidiasis, three out of four tested fluconazole-resistant clinical isolates did not exhibit a significant fitness defect. However, all four fluconazole-resistant isolates were outcompeted by the matched susceptible isolates in a mouse model of gastrointestinal colonization, demonstrating that the effects of drug resistance on in vivo fitness depend on the host niche. Collectively, our results indicate that the fitness costs of drug resistance in C. albicans are not easily remediated, especially when proper control of gene expression is required for successful adaptation to life within a mammalian host.

scholarly journals A Gain-of-Function Mutation in the Transcription Factor Upc2p Causes Upregulation of Ergosterol Biosynthesis Genes and Increased Fluconazole Resistance in a Clinical Candida albicans Isolate

2008 ◽  
Vol 7 (7) ◽  
pp. 1180-1190 ◽  
Author(s):  
Nico Dunkel ◽  
Teresa T. Liu ◽  
Katherine S. Barker ◽  
Ramin Homayouni ◽  
Joachim Morschhäuser ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Candida Albicans ◽  
Clinical Isolates ◽  
Resistant Isolate ◽  
Ergosterol Biosynthesis ◽  
Gain Of Function ◽  
Zinc Cluster ◽  
Fluconazole Resistant ◽  
Lanosterol Demethylase

ABSTRACT In the pathogenic yeast Candida albicans, the zinc cluster transcription factor Upc2p has been shown to regulate the expression of ERG11 and other genes involved in ergosterol biosynthesis upon exposure to azole antifungals. ERG11 encodes lanosterol demethylase, the target enzyme of this antifungal class. Overexpression of UPC2 reduces azole susceptibility, whereas its disruption results in hypersusceptibility to azoles and reduced accumulation of exogenous sterols. Overexpression of ERG11 leads to the increased production of lanosterol demethylase, which contributes to azole resistance in clinical isolates of C. albicans, but the mechanism for this has yet to be determined. Using genome-wide gene expression profiling, we found UPC2 and other genes involved in ergosterol biosynthesis to be coordinately upregulated with ERG11 in a fluconazole-resistant clinical isolate compared with a matched susceptible isolate from the same patient. Sequence analysis of the UPC2 alleles of these isolates revealed that the resistant isolate contained a single-nucleotide substitution in one UPC2 allele that resulted in a G648D exchange in the encoded protein. Introduction of the mutated allele into a drug-susceptible strain resulted in constitutive upregulation of ERG11 and increased resistance to fluconazole. By comparing the gene expression profiles of the fluconazole-resistant isolate and of strains carrying wild-type and mutated UPC2 alleles, we identified target genes that are controlled by Upc2p. Here we show for the first time that a gain-of-function mutation in UPC2 leads to the increased expression of ERG11 and imparts resistance to fluconazole in clinical isolates of C. albicans.

Antifungal Effects of Voriconazole-Loaded Nano-Liposome on Fluconazole-Resistant Clinical Isolates of Candida albicans, Biological Activity and ERG11, CDR1, and CDR2 Gene Expression

2021 ◽  
Vol 19 (7) ◽  
pp. 453-462
Author(s):  
Parviz Hassanpour ◽  
Hamed Hamishehkar ◽  
Behnaz Bahari Baroughi ◽  
Behzad Baradaran ◽  
Siamak Sandoghchian Shotorbani ◽  
...  
Keyword(s):  
Gene Expression ◽  
Biological Activity ◽  
Candida Albicans ◽  
Clinical Isolates ◽  
Antifungal Effects ◽  
Fluconazole Resistant

scholarly journals Antifungal Activity of Thai Cajuput Oil and Its Effect on Efflux-Pump Gene Expression in Fluconazole-Resistant Candida albicans Clinical Isolates

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Pitchayaphong Keereedach ◽  
Karnjana Hrimpeng ◽  
Khaemaporn Boonbumrung
Keyword(s):  
Gene Expression ◽  
Candida Albicans ◽  
Antifungal Activity ◽  
Efflux Pump ◽  
Clinical Problem ◽  
Antifungal Drugs ◽  
Clinical Isolates ◽  
Common Mechanism ◽  
Fluconazole Resistant ◽  
Resistant Strains

Candidiasis caused by the fluconazole-resistant opportunistic pathogen Candida albicans is an intractable clinical problem that threatens immunocompromised or normal individuals. The most common mechanism of fluconazole resistance in C. albicans is the failure of cells to accumulate the drug due to increased expression of the efflux proteins encoded by the CDR1, CDR2, and MDR1 genes. Because the number of current antifungal drugs is limited, it is necessary to develop new therapeutic strategies. This study aimed to evaluate the antifungal activity of Thai Cajuput oil, its synergism with fluconazole, and its effect on efflux-pump gene expression in fluconazole-resistant C. albicans clinical isolates. Thus, we first detected the efflux-pump genes in fourteen resistant strains by PCR. The frequencies of the CDR1, CDR2, and MDR1 genes were 68.75%, 62.5%, and 87.5%, respectively, and these efflux-pump genes were distributed in three distinct patterns. Subsequently, the antifungal activity of Thai Cajuput oil was assessed by broth macrodilution and its synergism with fluconazole was evaluated by the checkerboard assay. The changes in the expression levels of CDR1, CDR2, and MDR1 after treatment with Thai Cajuput oil were analyzed by qRT-PCR. The MICs and MFCs of Thai Cajuput oil ranged from 0.31 to 1.25 μl/ml and 0.63 to 1.25 μl/ml, respectively, and its activity was defined as fungicidal activity. The MICs of the combination of Thai Cajuput oil and fluconazole were much lower than the MICs of the individual drugs. Interestingly, sub-MICs of Thai Cajuput oil significantly reduced the MDR1 expression level in resistant strains P < 0.05 . Our study suggests that Thai Cajuput oil can be used to create new potential combination therapies to combat the antifungal resistance of C. albicans.

Efficacy of biogenic selenium nanoparticles against Leishmania major: In vitro and in vivo studies

2013 ◽  
Vol 27 (3) ◽  
pp. 203-207 ◽  
Author(s):  
Nasibeh Beheshti ◽  
Saied Soflaei ◽  
Mojtaba Shakibaie ◽  
Mohammad Hossein Yazdi ◽  
Fatemeh Ghaffarifar ◽  
...  
Keyword(s):  
Leishmania Major ◽  
Selenium Nanoparticles ◽  
In Vivo Studies ◽  
Biogenic Selenium Nanoparticles

scholarly journals Candida albicans Ferric Reductases Are Differentially Regulated in Response to Distinct Forms of Iron Limitation by the Rim101 and CBF Transcription Factors

2008 ◽  
Vol 7 (7) ◽  
pp. 1168-1179 ◽  
Author(s):  
Yong-Un Baek ◽  
Mingchun Li ◽  
Dana A. Davis
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Candida Albicans ◽  
Transcription Factors ◽  
Iron Acquisition ◽  
Mammalian Host ◽  
Regulatory Sequence ◽  
Ferric Reductase ◽  
Reductase Gene ◽  
Ferric Reductases

ABSTRACT Iron is an essential nutrient that is severely limited in the mammalian host. Candida albicans encodes a family of 15 putative ferric reductases, which are required for iron acquisition and utilization. Despite the central role of ferric reductases in iron acquisition and mobilization, relatively little is known about the regulatory networks that govern ferric reductase gene expression in C. albicans. Here we have demonstrated the differential regulation of two ferric reductases, FRE2 and FRP1, in response to distinct iron-limited environments. FRE2 and FRP1 are both induced in alkaline-pH environments directly by the Rim101 transcription factor. However, FRP1 but not FRE2 is also induced by iron chelation. We have identified a CCAAT motif as the critical regulatory sequence for chelator-mediated induction and have found that the CCAAT binding factor (CBF) is essential for FRP1 expression in iron-limited environments. We found that a hap5Δ/hap5Δ mutant, which disrupts the core DNA binding activity of CBF, is unable to grow under iron-limited conditions. C. albicans encodes three CBF-dependent transcription factors, and we identified the Hap43 protein as the CBF-dependent transcription factor required for iron-limited responses. These studies provide key insights into the regulation of ferric reductase gene expression in the fungal pathogen C. albicans.

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