Investigation of the Expression Levels of Efflux Pumps in Fluconazole-Resistant Candida albicans Isolates

2014 ◽  
Vol 48 (2) ◽  
pp. 325-334 ◽  
Author(s):  
Sinem GÜLAT ◽  
Mine DOLUCA DERELİ
Keyword(s):  
Candida Albicans ◽  
Efflux Pumps ◽  
Expression Levels ◽  
Fluconazole Resistant

scholarly journals Application of Real-Time Quantitative PCR to Molecular Analysis of Candida albicans Strains Exhibiting Reduced Susceptibility to Azoles

2004 ◽  
Vol 48 (6) ◽  
pp. 2124-2131 ◽  
Author(s):  
Andrew S. Chau ◽  
Cara A. Mendrick ◽  
Frank J. Sabatelli ◽  
David Loebenberg ◽  
Paul M. McNicholas
Keyword(s):  
Candida Albicans ◽  
Real Time ◽  
Quantitative Pcr ◽  
Efflux Pumps ◽  
Reference Points ◽  
Data Sets ◽  
Missense Mutations ◽  
Expression Levels ◽  
Real Time Quantitative Pcr ◽  
Genes Encoding

ABSTRACT Real-time quantitative PCR was used to measure expression levels of genes encoding efflux pumps, ERG11 and two control genes, ACT1 and PMA1, in a collection of 14 fluconazole-susceptible Candida albicans isolates. For each gene, average expression levels and variations within the population were determined. These values were then used as reference points to make predictions about the molecular basis of resistance in 38 clinical isolates (the majority of which were resistant to fluconazole) obtained from 18 patients treated with posaconazole for refractory oropharyngeal candidiasis. For each of the 38 isolates, the expression levels of genes encoding efflux pumps, ERG11 and the control genes, were measured as above. Comparison of the two data sets revealed that expression of ACT1 and PMA1 did not vary significantly between the two sets of isolates. In contrast, MDR1, ERG11, CDR1, and CDR2 were overexpressed in 3, 4, 14, and 35, respectively, of the isolates from patients treated with azoles. In addition to these changes, the patient isolates all had at least one and often multiple missense mutations in ERG11. Select ERG11 alleles were expressed in Saccharomyces cerevisiae; all of the alleles tested conferred reduced susceptibility to fluconazole. Despite both the increases in pump expression and the ERG11 mutations, only one of the patient isolates exhibited a large decrease in posaconazole susceptibility.

scholarly journals Synthetic Organotellurium Compounds Sensitize Drug-Resistant Candida albicans Clinical Isolates to Fluconazole

2016 ◽  
Vol 61 (1) ◽  
Author(s):  
L. F. Reis de Sá ◽  
F. T. Toledo ◽  
A. C. Gonçalves ◽  
B. A. Sousa ◽  
A. A. dos Santos ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Efflux Pumps ◽  
Major Facilitator Superfamily ◽  
Clinical Isolates ◽  
Multidrug Efflux ◽  
Fluconazole Resistance ◽  
Content Type ◽  
Multidrug Efflux Pumps ◽  
Fluconazole Resistant ◽  
Organotellurium Compounds

ABSTRACT Invasive Candida albicans infections are a serious health threat for immunocompromised individuals. Fluconazole is most commonly used to treat these infections, but resistance due to the overexpression of multidrug efflux pumps is of grave concern. This study evaluated the ability of five synthetic organotellurium compounds to reverse the fluconazole resistance of C. albicans clinical isolates. Compounds 1 to 4, at <10 μg/ml, ameliorated the fluconazole resistance of Saccharomyces cerevisiae strains overexpressing the major C. albicans multidrug efflux pumps Cdr1p and Mdr1p, whereas compound 5 only sensitized Mdr1p-overexpressing strains to fluconazole. Compounds 1 to 4 also inhibited efflux of the fluorescent substrate rhodamine 6G and the ATPase activity of Cdr1p, whereas all five of compounds 1 to 5 inhibited Nile red efflux by Mdr1p. Interestingly, all five compounds demonstrated synergy with fluconazole against efflux pump-overexpressing fluconazole-resistant C. albicans clinical isolates, isolate 95-142 overexpressing CDR1 and CDR2, isolate 96-25 overexpressing MDR1 and ERG11, and isolate 12-99 overexpressing CDR1, CDR2, MDR1, and ERG11. Overall, organotellurium compounds 1 and 2 were the most promising fluconazole chemosensitizers of fluconazole-resistant C. albicans isolates. Our data suggest that these novel organotellurium compounds inhibit pump efflux by two very important and distinct families of fungal multidrug efflux pumps: the ATP-binding cassette transporter Cdr1p and the major facilitator superfamily transporter Mdr1p.

Impact of Farnesol as a Modulator of Efflux Pumps in a Fluconazole-Resistant Strain of Candida albicans

2019 ◽  
Vol 25 (6) ◽  
pp. 805-812 ◽  
Author(s):  
Lucia Černáková ◽  
Stanislava Dižová ◽  
Dana Gášková ◽  
Iva Jančíková ◽  
Helena Bujdáková
Keyword(s):  
Candida Albicans ◽  
Resistant Strain ◽  
Efflux Pumps ◽  
Fluconazole Resistant

Expression of Major Efflux Pumps in Fluconazole-Resistant Candida albicans

2017 ◽  
Vol 17 (3) ◽  
Author(s):  
Babak Pourakbari ◽  
Mostafa Teymuri ◽  
Shima Mahmoudi ◽  
Sepideh K. Valian ◽  
Zahra Movahedi ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Efflux Pumps ◽  
Fluconazole Resistant

scholarly journals Suppression of Fluconazole Resistant Candida albicans Biofilm Formation and Filamentation by Methylindole Derivatives

2018 ◽  
Vol 9 ◽  
Author(s):  
Jin-Hyung Lee ◽  
Yong-Guy Kim ◽  
Vivek Kumar Gupta ◽  
Ranjith Kumar Manoharan ◽  
Jintae Lee
Keyword(s):  
Candida Albicans ◽  
Biofilm Formation ◽  
Fluconazole Resistant

scholarly journals A Combination Fluorescence Assay Demonstrates Increased Efflux Pump Activity as a Resistance Mechanism in Azole-Resistant Vaginal Candida albicans Isolates

2016 ◽  
Vol 60 (10) ◽  
pp. 5858-5866 ◽  
Author(s):  
Somanon Bhattacharya ◽  
Jack D. Sobel ◽  
Theodore C. White
Keyword(s):  
Candida Albicans ◽  
Efflux Pump ◽  
Pathogenic Fungus ◽  
Resistance Mechanism ◽  
Efflux Pumps ◽  
Resistant Isolate ◽  
Vaginal Infections ◽  
Content Type ◽  
Qrt Pcr ◽  
Pump Activity

ABSTRACTCandida albicansis a pathogenic fungus causing vulvovaginal candidiasis (VVC). Azole drugs, such as fluconazole, are the most common treatment for these infections. Recently, azole-resistant vaginalC. albicansisolates have been detected in patients with recurring and refractory vaginal infections. However, the mechanisms of resistance in vaginalC. albicansisolates have not been studied in detail. In oral and systemic resistant isolates, overexpression of the ABC transporters Cdr1p and Cdr2p and the major facilitator transporter Mdr1p is associated with resistance. Sixteen fluconazole-susceptible and 22 fluconazole-resistant vaginalC. albicansisolates were obtained, including six matched sets containing a susceptible and a resistant isolate, from individual patients. Using quantitative real-time reverse transcriptase PCR (qRT-PCR), 16 of 22 resistant isolates showed overexpression of at least one efflux pump gene, while only 1 of 16 susceptible isolates showed such overexpression. To evaluate the pump activity associated with overexpression, an assay that combined data from two separate fluorescent assays using rhodamine 6G and alanine β-naphthylamide was developed. The qRT-PCR results and activity assay results were in good agreement. This combination of two fluorescent assays can be used to study efflux pumps as resistance mechanisms in clinical isolates. These results demonstrate that efflux pumps are a significant resistance mechanism in vaginalC. albicansisolates.

scholarly journals Membrane fluidity and lipid composition of fluconazole resistant and susceptible strains of Candida albicans isolated from diabetic patients

2008 ◽  
Vol 39 (2) ◽  
pp. 219-225 ◽  
Author(s):  
Nagendra N. Mishra ◽  
Tulika Prasad ◽  
Neeraj Sharma ◽  
Dwijendra K. Gupta
Keyword(s):  
Candida Albicans ◽  
Membrane Fluidity ◽  
Lipid Composition ◽  
Diabetic Patients ◽  
Fluconazole Resistant
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