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

This work studied the impact of the quorum-sensing molecule, farnesol (FAR), on fluconazole (FLC)-resistant isolate CY 1123 compared with the susceptible standard strain 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 gene, are the main resistance mechanisms to azole antifungal drugs. The upregulation of genes coding for and were confirmed by qPCR with respect to the housekeeping gene in the resistant strain. The contribution of the gene was also observed. Markedly, increased pump activity (Cdr1 and/or Cdr2) in the CY 1123 strain was confirmed using diS-C(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 (MIC), 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 MIC shifted from 64 to 8 μg/mL. 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 isolates. However, this effect is dependent on FAR concentrations.