Characterisation and bioactivity evaluation of a frog-skin derived peptide, RT-5Cc, and its analogues, from the skin secretion of the American Bullfrog, Rana catesbeiana.

The increased charge in the modified peptide's sequence from 1 to 4 positively also affected its effectiveness against Gram-negative bacteria, especially Escherichia coli, without significant haemolysis. Moreover, results from the permeability and membrane potential suggested that the increased activity of 5Cc-modified peptides manifests in more pronounced disruption and damage to bacterial membranes. Optimizing AMP activity aims to apply it practically, especially in the context of the growing threat of AMR.

Chapter 5 delved into the synergistic effects of the modified peptides from Chapter 4 and four antibiotics. Results showed significant synergy, particularly between 5Cc-13/5Cc-63 and Rifampicin against Rifampicin-resistant Escherichia coli, lowering the antibiotic concentration and at least preventing the resistance growth. Subsequent experiments with the subsrate EtBr of influx and Efflux corroborate that bacterial resistance to Rifampicin is initially accompanied by reduced exposure of exogenous substances, which gradually decreases in efficiency as resistance develops.

Moreover, when administered in combination, AMPs and antibiotics elicit positive responses from increased drug retention purpose.<br><br> <i>Thesis is embargoed until 31 July 2029.</i>