Abstract
Candida krusei attracts attention from medical professionals mainly for its intrinsic resistance to fluconazole and the limited number of drugs available to treat C. krusei vulvovaginal candidiasis. Miltefosine was demonstrated to have good antifungal activity both in vitro and in vivo. Here, we determined the susceptibility profiles of 57 clinical C. krusei isolates from vulvovaginal candidiasis patients and assessed the antifungal activity of miltefosine against C. krusei. All isolates were susceptible to voriconazole and itraconazole, whereas 1.8% of the isolates were of non-wild-type phenotype to amphotericin B. In contrast, miltefosine showed low MICs against all C. krusei isolates with fungicidal activity. The checkerboard assay showed that the synergistic effect of miltefosine in combination with amphotericin B was observed in 25% of the tested planktonic C. krusei isolates and 18.8% of the tested preformed biofilms, whereas miltefosine in combination with fluconazole showed indifferent interaction for all tested planktonic isolates. The presence of sorbitol in the broth microdilution assay did not influence the MIC values of miltefosine against C. krusei, but the presence of ergosterol increased the MIC values. Visible changes in cell content in cells treated with miltefosine were observed. We found that cells treated with miltefosine showed decreased cell viability and chromatin condensation under PI staining, which indicates that miltefosine may induce apoptosis-like cell death in C. krusei. In conclusion, we found miltefosine has a good activity against C. krusei isolates and exerts its fungicidal effect by binding to ergosterol in the cell membrane and inducing apoptosis.
Highlights
Pathogenic Candida species can cause invasive candidiasis that takes more than 50,000 lives worldwide annually, and it causes recurrent vulvovaginal candidiasis that affects approximately 138 million women annually (Kullberg and Arendrup, 2015; Denning et al, 2018)
We assessed the susceptibility of azoles and amphotericin B against C. krusei isolates from patients with vulvovaginal candidiasis
We found all isolates were susceptible and of wild type to voriconazole and itraconazole, respectively, which is consistent with other reports on the susceptibility of isolates from invasive candidiasis patients (Gong et al, 2018)
Summary
Pathogenic Candida species can cause invasive candidiasis that takes more than 50,000 lives worldwide annually, and it causes recurrent vulvovaginal candidiasis that affects approximately 138 million women annually (Kullberg and Arendrup, 2015; Denning et al, 2018). Antifungal Activity of Miltefosine Against Candida krusei way of controlling vulvovaginal candidiasis caused by fluconazole-resistant Candida species is an important problem because there are only a few effective therapeutic drugs that can be used on vulvovaginal candidiasis patients (Sobel, 2016; Sobel and Sobel, 2018). Echinocandins such as caspofungin are currently the drugs of choice for treatment of invasive C. krusei candidiasis infections, echinocandin-resistant isolates caused by point mutations in the FKS1 gene have increased (Jensen et al, 2014; Forastiero et al, 2015; Lallitto et al, 2018). It has become essential to develop antifungal agents with novel antifungal mechanisms for the treatment of candidiasis caused by C. krusei
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