Combined effect of lasioglossin LL-III derivative with azoles against Candida albicans virulence factors: biofilm formation, phospholipases, proteases and hemolytic activity

• Published in: FEMS yeast research Vol. 20; no. 3; pp. 1 - 16
• Main Authors: Vankova, Eva, Kasparova, Petra, Dulickova, Nikola, Cerovsky, Vaclav
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.05.2020
• Subjects: Antimicrobial agents; Antimicrobial peptides; Azoles; Biofilms; Bone surgery; Candida albicans; Catheters; Clotrimazole; Mushrooms; Peptides; Phospholipases; Proteases; Scanning electron microscopy; Surgery; Virulence factors; Czech Republic; Candida albicans; biofilm formation; azoles; antimicrobial peptides; virulence factors; LL-III derivative
• ISSN: 1567-1364; 1567-1356; 1567-1364
• DOI: 10.1093/femsyr/foaa020

Candida albicans has several virulence factors at its disposal, including yeast-hyphal transition associated with biofilm formation, phospholipases, proteases and hemolytic activity, all of which contribute to its pathogenesis. We used synthetic derivative LL-III/43 of antimicrobial peptide lasioglossin LL-III to enhance effect of azoles on attenuation of C. albicans virulence factors. LL-III/43 was able to inhibit initial adhesion or biofilm formation of C. albicans strains at 50 µM. Azoles, however, were ineffective at this concentration. Using fluorescently labeled LL-III/43, we observed that peptide covered C. albicans cells, partially penetrated through their membranes and then accumulated inside cells. LL-III/43 (25 µM) in combination with clotrimazole prevented biofilm formation already at 3.1 µM clotrimazole. Neither LL-III/43 nor azoles were able to significantly inhibit phospholipases, proteases, or hemolytic activity of C. albicans. LL-III/43 (25 µM) and clotrimazole (50 µM) in combination decreased production of these virulence factors, and it completely attenuated its hemolytic activity. Scanning electron microscopy showed that LL-III/43 (50 µM) prevented C. albicans biofilm formation on Ti-6Al-4 V alloy used in orthopedic surgeries and combination of LL-III/43 (25 µM) with clotrimazole (3.1 µM) prevented biofilm formation on urinary catheters. Therefore, mixture of LL-III/43 and clotrimazole is suitable candidate for future pharmaceutical research.