Minimum inhibitory concentrations of amphotericin B, azoles and caspofungin against Candida species are reduced by farnesol.
The objective of this study was to evaluate the antifungal activity of farnesol and its interaction with traditional antifungals against drug-resistant strains of Candida species. To do so, we studied the minimum in vitro inhibitory concentration (MIC) of amphotericin B (AMB), fluconazole (FLC), itraconazole (ITC), caspofungin (CAS) and farnesol against 45 isolates of Candida spp., i.e., 24 C. albicans, 16 C. parapsilosis and 5 C. tropicalis through the use of the broth microdilution method. Then, the isolates were tested with the combination of farnesol plus drugs to which they were previously found to be resistant. Additionally, the strains were pre-incubated at sub-inhibitory farnesol concentrations and their antifungal susceptibilities were re-evaluated. We found the MIC values for farnesol varied from 4.68-150 µM for Candida spp., with 19 isolates having a MIC > 1 mg/l, 18 a MIC ≥ 64 mg/l, 35 having a MIC ≥ 1 mg/l and 6 isolates a MIC ≥ 2 mg/l or were resistant to AMB, FLC, ITC and CAS, respectively. Significant MIC reductions were observed when farnesol and antifungal drugs were combined (P < 0.05) and when Candida strains were incubated with farnesol (P < 0.05). We conclude that the in vitro effects of farnesol improved the activity of traditional antifungals to which the Candida spp. isolates were resistant. These results support further investigation of the role of farnesol in the balance of the sterol biosynthetic pathway and how it interferes with cell viability.
Department of Pathology and Legal Medicine, College of Medicine, Postgraduate Program in Medical Microbiology, Specialized Medical Mycology Center, Federal University of Ceará, Fortaleza, Ceará, Brazil.
Rossana A
RA
Cordeiro
Carlos E C
CE
Teixeira
Raimunda S N
RS
Brilhante
Débora S C M
DS
Castelo-Branco
Manoel A N
MA
Paiva
João J
JJ
Giffoni Leite
Daniel T
DT
Lima
André J
AJ
Monteiro
José J C
JJ
Sidrim
Marcos F G
MF
Rocha
D000666:Amphotericin B / Q000494:pharmacology; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D002175:Candida / Q000187:drug effects* / Q000302:isolation & purification; D002177:Candidiasis / Q000382:microbiology*; D000077336:Caspofungin; D025141:Drug Resistance, Fungal / Q000187:drug effects; D004357:Drug Synergism; D054714:Echinocandins / Q000494:pharmacology; D005204:Farnesol / Q000494:pharmacology*; D015725:Fluconazole / Q000494:pharmacology; D006801:Humans; D017964:Itraconazole / Q000494:pharmacology; D055666:Lipopeptides; D008826:Microbial Sensitivity Tests
D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D017964:Itraconazole; D005204:Farnesol; D000666:Amphotericin B; D015725:Fluconazole; D000077336:Caspofungin