Amphibians have developed numerous strategies to fight against their predators and the invasion of microorganisms by producing noxious/toxic skin secretions. Amphibian skins have been targeted for different kinds of medicinal substances in Traditional Chinese Medicine since ancient times. Many more pathogens are developing resistance to conventional antibiotics, and the novel putative antibiotics are failing in the fight against bacteria. Therefore there is an urgent need for new antibiotic resources. From previous studies, the amphibian defensive skin secretions and scorpion venom have proven to be great treasury for novel functional peptide discovery and these have become attractive targets for innovative drug development. In Chapter 3, an antimicrobial peptide (Phylloseptin-PHa) from the phylloseptin family was employed to investigate the structure-activity relationship, and the balance of hydrophobicity and charge determines the selectivity of bioactivities, at which point it is feasible to design a peptide as alternative to conventional antibiotics. In Chapter 4, a novel potential antimicrobial peptide with the highly-conserved primary structure of phylloseptin peptide, named Phylloseptin-PDu (PSPDu), was identified and characterized from the skin secretion of a Hylidae frog, Phyllomedusaduellmani, using the ‘shotgun’ molecular cloning strategy and mass spectrometry. PSPDu exhibited a broad-spectrum antimicrobial activity against seven selected microorganisms, subsequently, based on the previous study ofChapter3, PSPDu was employed as a template to design a novel peptide Art-PSPDu, which is a nearly-perfect antimicrobial peptide exhibiting an enhanced antimicrobial activity against microorganisms with a significantly decreased cytotoxicity. In Chapter 5, a novel antimicrobial peptide was identified and characterised from the venom of the scorpion, Androctonus australis. Hector, using the ‘shotgun’ molecular cloning strategy and mass spectrometry. Subsequently, several analogues were designed to investigate the relationship between cationicity and C-terminal amidation. Hence, the results indicate that increasing the net charges on the traditional antibiotics may be an alternative method to enhance the activity of antibiotics against resistant bacteria.
Thesis is embargoed until 31 May 2024.
|Date of Award||2019|
|Supervisor||Tianbao Chen (Supervisor), Mei Zhou (Supervisor), Lei Wang (Supervisor) & Xinping Xi (Supervisor)|