A pilot study on ultrashort peptide with fluconazole: A promising novel anticandidal combination

Abstract

Background and Aim: Human infections caused by Candida albicans are common and range in severity from relatively treatable skin and mucosal conditions to systemic, fatal invasive candidiasis. The treatment of fungal infections is challenged by major obstacles, including the scarcity of effective therapeutic options, the toxicity of available medications, and the escalating antifungal resistance. Hence, there exists an urgent need to develop new classes of antimicrobial agents. This study was conducted to investigate the effect of KW-23 peptide against standard and resistant strains of C. albicans alone and in combination with fluconazole. Materials and Methods: A conjugated ultrashort antimicrobial peptide (KW-23) was designed and synthesized. KW-23 was challenged against standard and multidrug-resistant C. albicans alone and in combination with fluconazole using standard antimicrobial and checkerboard assays. The toxicity of the peptide was examined using hemolytic assays. Results: KW-23 positively affected the standard and resistant Candidal strains (at 5 and 15 µg/mL respectively), exhibiting potent synergistic antimicrobial activity against the standard strain when combined with fluconazole. The effect of the combination was additive against the resistant strain (0.6 µg/mL). Furthermore, the peptide exhibited negligible toxicity on human erythrocytes. Conclusion: KW-23 and its combination with fluconazole could be a promising candidate for developing anticandidal agents. Keywords: Candida albicans, drug combinations, fluconazole, synergism, ultrashort peptide.