Impact of Farnesol as a Modulator of Efflux Pumps in a Fluconazole-Resistant Strain of <i>Candida albicans</i>

Abstract

<b><i>Aim:</i></b> This work studied the impact of the quorum-sensing molecule, farnesol (FAR), on fluconazole (FLC)-resistant <i>Candida albicans</i> isolate CY 1123 compared with the susceptible standard strain <i>C. albicans</i> SC5314. The genes encoding efflux pumps belonging to the ATP-binding cassette (ABC) and major facilitator superfamilies, together with overexpression or point mutation of the <i>ERG11</i> gene, are the main resistance mechanisms to azole antifungal drugs. <b><i>Results:</i></b> The upregulation of genes coding for <i>CDR1, CDR2,</i> and <i>MDR1</i> were confirmed by qPCR with respect to the housekeeping gene <i>ACT1</i> in the resistant strain. The contribution of the <i>ERG11</i> gene was also observed. Markedly, increased pump activity (Cdr1 and/or Cdr2) in the CY 1123 strain was confirmed using diS-C₃(3) assay. However, the addition of FAR to the yeasts diminished the difference in staining levels between the SC5314 and CY 1123 strains, demonstrating the concentration-dependent character that could be caused by an effective modulation of Cdr pumps. FAR (60 and 100 μM) was also able to decrease the minimal inhibitory concentrations (MIC₅₀), denoting the inhibition of planktonic cells by 50%, from 8 to 4 μg/mL of FLC when the resistant strain CY 1123 was not cultivated with FLC. However, when it was exposed to 64 μg/mL of FLC, the MIC₅₀ shifted from 64 to 8 μg/mL. <b><i>Conclusion:</i></b> Besides the many other effects of FAR on eukaryotic and prokaryotic cells, it also affects ABC efflux transporters, resulting in changes in resistance to azoles in <i>C. albicans</i> isolates. However, this effect is dependent on FAR concentrations.