Combined effect of lasioglossin LL-III derivative with azoles against Candida albicans virulence factors: biofilm formation, phospholipases, proteases and hemolytic activity
Language English Country Great Britain, England Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
32324227
DOI
10.1093/femsyr/foaa020
PII: 5824167
Knihovny.cz E-resources
- Keywords
- Candida albicans, LL-III derivative, antimicrobial peptides, azoles, biofilm formation, virulence factors,
- MeSH
- Antifungal Agents pharmacology MeSH
- Azoles pharmacology MeSH
- Biofilms drug effects growth & development MeSH
- Candida albicans drug effects MeSH
- Erythrocytes drug effects MeSH
- Virulence Factors MeSH
- Phospholipases antagonists & inhibitors MeSH
- Hemolysis drug effects MeSH
- Hydrophobic and Hydrophilic Interactions drug effects MeSH
- Antimicrobial Cationic Peptides chemical synthesis pharmacokinetics MeSH
- Humans MeSH
- Peptide Hydrolases metabolism MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Antifungal Agents MeSH
- Azoles MeSH
- Virulence Factors MeSH
- Phospholipases MeSH
- Antimicrobial Cationic Peptides MeSH
- lasioglossin III MeSH Browser
- Peptide Hydrolases MeSH
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.
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