Amphibian-derived peptide analog TB_KKG6K: A powerful drug candidate against Candida albicans with anti-biofilm efficacy

Candida albicans , a commensal and opportunistic fungal pathogen, is a major clinical concern due to its ability to cause infections ranging from mild mucosal conditions to life-threatening systemic diseases, particularly in immunocompromised patients. Its capacity to form biofilms on medical devices further complicates treatment by enhancing antifungal resistance and immune evasion. In the search for novel therapeutic strategies, the lysine-enriched amphibian-derived temporin B analog, TB_KKG6K, has emerged as a promising antifungal agent. This study demonstrates that TB_KKG6K exhibits potent activity against planktonic C. albicans cells, with a low potential to induce adaptation or resistance, even after prolonged exposure. TB_KKG6K has no adverse impact on the anti- Candida efficacy of standard antifungal drugs like amphotericin B, caspofungin, fluconazole or 5-flucytosine, when applied in combination. Additionally, TB_KKG6K effectively reduces biofilm maturation on silicone elastomers, a material commonly used in medical devices, further highlighting its therapeutic potential. These data together with our previous documentation of minimal cytotoxicity and irritation potential in human cells, makes TB_KKG6K a strong candidate for combating both planktonic and biofilm-associated C. albicans infections. These findings underscore the dual efficacy of TB_KKG6K and its potential to address the challenges posed by C. albicans in clinical settings.