Wenyi Li group
Chemical Biology, Peptide Chemistry
Antimicrobial peptides (AMPs), known as host defence peptides, are potentially potent alternatives to conventional antibiotics, given their broad spectrum of activity. They mainly interact with cell membranes through surface electrostatic potentials and the formation of secondary structures, resulting in permeability and destruction of target microorganism membranes. To further improve the antibacterial activity, we have applied different chemical modifications on several AMPs, including multimerisation, conjugation and lipidation. For example, the attachment of moderate-length lipid carbon chains to cationic peptides can assist peptide insertion into the membrane lipid bilayer, inducing curvature and resulting in membrane pore formation, destabilisation, depolarisation, and leakage. Our findings highlight the advantages of modern chemical biology methods in developing novel AMPs with more potent antibacterial activity.
In addition, the plant defensins are widely dispersed across the plant kingdom and are significant components of the plant’s innate immune system. Interestingly, unlike those found in insects and mammals, plant defensins commonly target fungi rather than bacteria. We are currently modifying a series of chimaera plant defensins to investigate their structure and antimicrobial activity against both bacteria and fungi. The knowledge generated will direct the novel antifungal/antibacterial design and combination therapies against infections.
RESEARCH AREAS
Chronic wound infections are major complications of Diabetes mellitus and are responsible for significant morbidity and mortality. Over 50% of diabetes patients with Diabetic foot ulcers (DFUs) are estimated to develop diabetic foot infections by a polymicrobial community of microorganisms with wound chronicity. The increasing resistance of pathogens to antibiotics causes a huge clinical burden that places great demands on academic researchers and the pharmaceutical industry for resolution. Previously, we identified two leading AMPs that possess effective antibacterial activity against bacteria, including Escherichia coli and S. aureus. More recently, our recent study showed that the chemical modification enhanced their antibacterial activity against pathogens, but also increased their cytotoxicity. In this project, we will develop novel potent AMPs against DFI pathogens with wound healing properties on innovative chronic wound models.
The plant defensins are widely dispersed across the plant kingdom and are significant components of the plant’s innate immune system. The plant defensins exhibit potent antimicrobial properties, containing 6–8 cysteine residues capable of forming 2–6 disulfide bridges with 7 loops, which provide the molecules with high chemical and thermal stability. Our current data showed that a specific group of plant defensins had very potent antibacterial activity against MDR bacteria. Importantly, we have found the modulation of defensins can enhance their antifungal activity and antibacterial activity. Thus, we are currently modifying a series of plant defensins to investigate their structure and antimicrobial activity against both bacteria and fungi. The knowledge generated will direct the novel antifungal/antibacterial design and combination therapies against infections.
Meet the team
Group Leader:
- Dr Wenyi Li
PhD researchers:
- Ms Tianmeng Zhang (2027)
- Mr Yujie Zhu (2027)
- Mr Meet Parmar (2028)
Honours researchers:
- Mr Aydin Menekse (2026)
Research officer:
- Dr Praveen Praveen