DOI: 10.1002/psc.70117 ISSN: 1075-2617
Gold Nanoparticles Coated With the Antimicrobial Peptide Os‐C(W5): Anticandidal and Biological Activity
P. J. Palm, R. R. Chirombo, C. K. Chiramba, J. C. Serem, H. Taute, M. van der Walt, A. R. M. Gaspar, M. J. Bester ABSTRACT
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(W
5
) which improved antifungal activity and reduced salt sensitivity; however, the proteolytic susceptibility of Os‐C(W
5
) 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(W
5
). GNP@Os‐C(W
5
) 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(W
5
), GNP@Os‐C(W
5
) 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(W
5
) and GNP@Os‐C(W
5
) were non‐cytotoxic to HaCat cells. Most importantly, resistance to the protease trypsin was increased. However, antioxidant properties of Os‐C(W
5
) were lost with GNP conjugation, whereas both Os‐C(W
5
) and GNP@Os‐C(W
5
) 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(W
5
) to reduce oxidative stress was compromised.