Gold Nanoparticles Coated With the Antimicrobial Peptide Os-C(W5): Anticandidal and Biological Activity

Candida albicans is a critical-priority fungal pathogen due to its global burden of infection, biofilm-forming ability, and increasing drug resistance. Previously, the tick-derived antimicrobial peptide (AMP), Os-C, demonstrated antifungal, antioxidant, and nitric oxide (NO) scavenging activity. Subsequent tryptophan end-tagging produced Os-C(W₅) which improved antifungal activity and reduced salt sensitivity; however, the proteolytic susceptibility of Os-C(W₅) remained a limitation. Researchers have shown that N-terminal tryptophan tagging of a gold binding peptide generated gold nanoparticle (GNPs) of a clinically relevant size. We successfully applied this method with minor modifications to generate GNPs coated with Os-C(W₅). GNP@Os-C(W₅) exhibited an average diameter of 14.2 ± 0.32 nm, with preserved peptide disorder in peptide secondary structure after conjugation. Compared with free Os-C(W₅), GNP@Os-C(W₅) activity against planktonic C. albicans was reduced, but antibiofilm activity was maintained, associated with a reduction in biofilm biomass. Ultrastructural changes to planktonic C. albicans included roughened and irregular surfaces, membrane indentations, and extracellular debris indicating cell lysis. Samples treated with Os-C(W5) and GNP@Os-C(W5) showed visibly less dense biofilm architecture and fewer apparent hyphal structures relative to the untreated control. Both Os-C(W₅) and GNP@Os-C(W₅) were non-cytotoxic to HaCat cells. Most importantly, resistance to the protease trypsin was increased. However, antioxidant properties of Os-C(W₅) were lost with GNP conjugation, whereas both Os-C(W₅) and GNP@Os-C(W₅) compared with Os-C lacked NO scavenging activity. Overall, this method of GNP conjugation provides a viable strategy to achieve enhanced AMP stability, retained antifungal activity, although the ability of GNP@Os-C(W₅) to reduce oxidative stress was compromised.