Monitoring of energy-dependent efflux in Candida albicans
Author | Affiliation | |
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LT | ||
Date |
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2018 |
Patients with AIDS and those who are undergoing chemotherapeutic modalities are always at a risk of developing C. albicans infections. Morbidity and mortality from invasive candidiasis and candidemia have increased significantly over the last four decades. The scientific and clinical findings have shown that the incidence of severe Candida infections is constantly increasing. With the development of azoles and other antifungal medicines, the potential for treatment of these infections has improved significantly. However, the possibility of timely diagnosis of fungal infections is limited, and therefore the outcome of the disease is not favorable. The pivotal membrane transporters that C. albicans is exploiting as one of the strategies to develop multidrug resistance (MDR), belong to either the ATP binding cassette (ABC) or the major facilitator superfamily (MFS) classes of efflux pumps. Overexpression of the efflux pumps Cdr1p, Cdr2p and Mdr1p is the main mechanism of fluconazole resistance in C. albicans. For studies of yeast efflux activity we applied electrochemical measurements of phenyldicarbaundeborane (PCB-) ions in incubation medium. To activate the MDR pumps C. albicans wild-type cells were cultivated with fluconazole. During experiments in arsenate buffer, where the cells rapidly lose ATP, an additional binding of PCB- is observed. This indicates the suspended activity of cellular MDR pumps due to the lack of energy. No additional accumulation of PCB- was observed in experiments with control cells grown without fluconazole. Using this assay method different C. albicans isolates were investigated and the results of this study will be presented at the conference.