The Inhibitory Effect of Human Beta-defensin-3 on Candida Glabrata Isolated from Patients with Candidiasis

Abstract Candida glabrata is a common non-albicans Candida species found in patients with candidiasis and it sometimes develops antifungal resistance. Human beta-defensin-3 (hBD-3) is an antimicrobial peptide of immune system active against various types of microbes including Candida spp. This study investigated antifungal activity of hBD-3 and its synergistic effect with a first-line antifungal agent on C. glabrata clinical isolates. Candida spp. were characterised in patients with candidiasis. The antifungal activities of hBD-3 and fluconazole against C. glabrata were evaluated using Broth microdilution assay. The synergistic activity of these two agents was determined by checkerboard microdilution and time-killing assays. The cytotoxicity of hBD-3 was evaluated using LDH-cytotoxicity colorimetric assay. Of 307 episodes from 254 patients diagnosed with candidiasis, C. glabrata was found in 21 clinical isolates. Antifungal susceptibility tests of C. glabrata were performed, fluconazole demonstrated an inhibitory effect at concentrations of 0.25-8 μg/ml, but one antifungal resistant strain was identified (>64 μg/ml). hBD-3 showed an inhibitory effect against all selected strains at concentrations of 50-75 μg/ml and exhibited a synergistic effect with fluconazole at the fractional inhibitory concentration index (FICI) of 0.25-0.50. A concentration of 25 μg/ml of hBD-3 alone showed no cytotoxicity but synergistic activity was seen with fluconazole. In conclusion, hBD-3 has antifungal activity against C. glabrata and synergistic effects with fluconazole at concentrations that alone, have no cytotoxicity. hBD-3 could be used as an adjunctive therapy with first-line antifungal agents for patients with C. glabrata infection particularly those infected with fluconazole-resistant strains.

วารสาร : Immunol Invest . 2021 Jan;50(1):80-91. doi: 10.1080/08820139.2020.1755307. Epub 2020 Apr 22

Keyword : candida glabrata; Human beta-defensin; candidiasis