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In vitro and in vivo effects of suloctidil on growth and biofilm formation of the opportunistic fungus Candida albicans .
Oncotarget 2017 September 20
As the most frequent fungal pathogen in humans, Candida albicans can develop serious drug resistance because its biofilms are resistant to most antifungal agents; this leads to an urgent need to develop novel antifungals. Here, we evaluated the efficacy of an antithrombotic drug, suloctidil, against C. albicans biofilms in vitro and in vivo . We found that suloctidil is effective to inhibit C. albicans biofilm, with a minimum inhibitory concentration (MIC80 ) of 4 μg/mL, a biofilm inhibiting concentration (BIC80 ) of 16 μg/mL and a biofilm eradicating concentration (BEC80 ) of 64 μg/mL. Furthermore, the concentration-dependent characteristics of suloctidil were shown by its time-kill curves. Scanning electron microscopy images clearly revealed the morphological effects of suloctidil on biofilm. Yeast-to-hyphal form switching is a key virulence factor of C. albicans ; therefore, we performed hyphal growth tests and observed that suloctidil inhibited yeast-to-hyphal form switching. This result was consistent with the down-regulation of hypha-specific gene ( HWP1, ALS3 , and ECE1 ) expression levels after suloctidil treatment. In vivo , 256 μg/mL of suloctidil significantly reduced fungal counts ( P <0.01) compared to that in groups without treatment; the treatment group induced a slight histological reaction, especially when the treatment lasted for 5 days ( P <0.01). Taken together, our data suggest that suloctidil is a potential antifungal agent.
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