Troskie Anscha Mari, Rautenbach Marina, Delattin Nicolas, Vosloo Johan Arnold, Dathe Margitta, Cammue Bruno P A, Thevissen Karin
BIOPEP Peptide Group, Department of Biochemistry, Science Faculty, University of Stellenbosch, Stellenbosch, South Africa.
Centre of Microbial and Plant Genetics, CMPG, KU Leuven, Heverlee, Belgium.
Antimicrob Agents Chemother. 2014 Jul;58(7):3697-707. doi: 10.1128/AAC.02381-14. Epub 2014 Apr 21.
Tyrocidines are cationic cyclodecapeptides from Bacillus aneurinolyticus that are characterized by potent antibacterial and antimalarial activities. In this study, we show that various tyrocidines have significant activity against planktonic Candida albicans in the low-micromolar range. These tyrocidines also prevented C. albicans biofilm formation in vitro. Studies with the membrane-impermeable dye propidium iodide showed that the tyrocidines disrupt the membrane integrity of mature C. albicans biofilm cells. This membrane activity correlated with the permeabilization and rapid lysis of model fungal membranes containing phosphatidylcholine and ergosterol (70:30 ratio) induced by the tyrocidines. The tyrocidines exhibited pronounced synergistic biofilm-eradicating activity in combination with two key antifungal drugs, amphotericin B and caspofungin. Using a Caenorhabditis elegans infection model, we found that tyrocidine A potentiated the activity of caspofungin. Therefore, tyrocidines are promising candidates for further research as antifungal drugs and as agents for combinatorial treatment.
短杆菌酪肽是来自解硫胺素芽孢杆菌的阳离子环十肽，具有强大的抗菌和抗疟活性。在本研究中，我们表明，各种短杆菌酪肽在低微摩尔范围内对浮游白色念珠菌具有显著活性。这些短杆菌酪肽还能在体外阻止白色念珠菌生物膜的形成。使用膜不可渗透的染料碘化丙啶进行的研究表明，短杆菌酪肽会破坏成熟白色念珠菌生物膜细胞的膜完整性。这种膜活性与短杆菌酪肽诱导的含磷脂酰胆碱和麦角固醇（比例为70:30）的模型真菌膜的通透性增加和快速裂解相关。短杆菌酪肽与两种关键抗真菌药物两性霉素B和卡泊芬净联合使用时，表现出显著的协同生物膜根除活性。使用秀丽隐杆线虫感染模型，我们发现短杆菌酪肽A增强了卡泊芬净的活性。因此，短杆菌酪肽作为抗真菌药物和联合治疗药物，是有前景的进一步研究候选物。
