Title |
The in vitro and in vivo efficacy of fluconazole in combination with farnesol against Candida albicans isolates using a murine vulvovaginitis model |
Author |
Aliz Bozó1, Marianna Domán1, László Majoros1, Gábor Kardos1, István Varga2, and Renátó Kovács1* |
Address |
1Department of Medical Microbiology, Faculty of Medicine, University of Debrecen, Debrecen 4032, Hungary, 2Department of Periodontology, Faculty of Dentistry, University of Debrecen, Debrecen 4032, Hungary |
Bibliography |
Journal of Microbiology, 54(11),753-760, 2016,
|
DOI |
10.1007/s12275-016-6298-y
|
Key Words |
time-kill experiment, FIC index, murine vulvovaginitis,
fluconazole-resistant, synergy |
Abstract |
Farnesol is a quorum-sensing molecule that inhibits biofilm
formation in Candida albicans. Previous in vitro data suggest
that, in combination with certain antifungals, farnesol
may have an adjuvant anti-biofilm agent. However, the in
vivo efficacy of farnesol is very questionable. Therefore, the
in vitro and in vivo activity of fluconazole combined with farnesol
was evaluated against C. albicans biofilms using fractional
inhibitory concentration index (FICI) determination,
time-kill experiments and a murine vulvovaginitis model.
The median biofilm MICs of fluconazole-sensitive C. albicans
isolates ranged between 4 -> 512 mg/L and 150–300 μM
for fluconazole and farnesol, respectively. These values were
512 -> 512 mg/L and > 300 μM for fluconazole-resistant clinical
isolates. Farnesol decreased the median MICs of fluconazole
by 2-64-fold for biofilms. Based on FICI, synergistic
interaction was observed only in the case of the sessile
SC5314 reference strain (FICIs: 0.16–0.27). In time-kill studies,
only the 512 mg/L fluconazole and 512 mg/L fluconazole
+ 75 μM farnesol reduced biofilm mass significantly at
each time point in the case of all isolates. The combination
reduced the metabolic activity of biofilms for all isolates in a
concentration- and time-dependent manner. Our findings
revealed that farnesol alone was not protective in a murine
vulvovaginitis model. Farnesol was not beneficial in combination
with fluconazole for fluconazole-susceptible isolates,
but partially increased fluconazole activity against one fluconazole-
resistant isolate, but not the other one. |