Browsing by Author "De Villiers, Carmen"
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- ItemMetal and tyrocidine nano-assemblies to create broadspectrum metal-peptide formulations(Stellenbosch : Stellenbosch University, 2023-03) De Villiers, Carmen; Rautenbach, Marina; Stellenbosch University. Faculty of Science. Dept. of Biochemistry.ENGLISH ABSTRACT: Without the discovery or development of novel drugs, the phenomena of antimicrobial resistance (AMR) will continue to threaten the effective treatment of pathogenic microbes and diseases across the globe. Combinational therapies of antimicrobial peptides (AMPs) with metal nanoparticles (MNPs) have shown promise for the creation of potent nano- drugs with broad spectrum antimicrobial activity, alternative applications, and lowered risk of resistance development. In this study the combinational formulation of biologically relevant metals (magnesium, calcium, iron, copper, silver, gold, and zinc) with a group of natural antimicrobial cyclodecapeptides (CDPs) was investigated for the fabrication of potent AMP-MNP nanodrugs. The CDPs selected for this study include an aromatic residue rich peptide complex (tyrocidine mixture, Trc mix) and tryptophan rich purified analogues (tyrocidine C, TrcC and tryptocidine C, TpcC). Mass spectrophotometric studies revealed that these peptides form peptide-metal complexes with certain metals, and that the absence or presence of such complexes in formulations altered the peptides oligomerisation behaviour. Although formulations with group 11 metals lacked peptide- metal complexes, changes in peptide oligomerisation and analogue-specific prevalence was observed. Since the aromatic rich structure of these CDPs holds potential for synthesis of MNPs, it was hypothesised that the absence of peptide-metal complexes in group 11 formulations is likely due to the reduction of metal ions and formation of MNPs. This hypothesis was confirmed by spectrophotometric and spectrofluorometric studies which reported the formation of silver nanoparticles (AgNPs) in Trc mix, TpcC and TrcC formulations with silver. These studies also indicated alterations in peptide conformation when in formulation and highlighted the critical role of tryptophan for successful CDP- AgNP fabrication. Scanning transmission microscopy revealed that the peptide- synthesised spherical AgNPs were encapsulated by CDP nanostructures, a promising conjugate structure for drug delivery. Solid surface antimicrobial assays and reported additive and synergistic antimicrobial actions between CDPs and MNPs against model organisms, Gram positive Staphylococcus aureus and Gram-negative Escherichia coli, respectively. The innate self-assembly of these aromatic amino acid rich CDPs therefore holds potential to streamline the synthesis of potent yet versatile CDP-MNP nanoformulations for topical or antimicrobial surface treatments against Gram-positive and Gram-negative bacteria. Moreover, unprecedented antibacterial activity was also reported for TpcC, which could have applications in future therapies.