Research Leader: Prof A Gaspar

Background:
Antimicrobial peptides (AMPs) are key components of the innate immune system of living organisms and promising alternatives to current antibiotics. These peptides have numerous attractive properties including broad-spectrum activity, rapid onset of killing, bactericidal and/or immunomodulatory capabilities, biofilm disruption, and low incidence of resistance development. Challenges associated with AMPs are their susceptibility to proteolytic degradation, cytotoxicity to eukaryotic cells, reduced efficacy under certain physiological conditions and high production costs. These limitations can be overcome by designing shorter analogues and structure modification.
Currently, the research focus is the development of AMP-based antibiotics targeting Gram-negative resistant pathogens. The project is funded by the UK-SAMRC and is conducted in collaboration with co-investigators at UP, UCT (H3D) and in the UK. Novel AMPs targeting Gram-negative bacteria have been identified by screening a large panel of AMPs (tick, scorpion, frog, primate). For the rational design of analogues with improved activity and reduced cytotoxicity, molecular dynamics simulations are performed to better understand the interactions of identified AMPs with model Gram- negative bacterial membranes. Promising AMPs are evaluated for toxicity and potential for topical or systemic application using ex vivo porcine cornea and in vivo Galleria mellonella infection models.

Team

Research Leader
Prof Anabella Gaspar Google Scholar ORCiD
Postdoctoral Researcher
Dr Auwal Ibrahim
PhD Candidates
Court Chiramba	Dalton Möller	Mandelie van der Walt	Rosalind van Wyk
MSc Candidates
Molebogeng Onkaetse	Kabelo Sitwe	Janeska van Heerden

Collaborators:

• Prof Yasien Sayed, University of the Witwatersrand, South Africa

• Dr Adam Strömstedt, Uppsala University, Sweden

Recent Publications:

1. MBUAYAMA KR, TAUTE H, STRÖMSTEDT AA, BESTER MJ & GASPAR ARM (2022). Antifungal activity and mode of action of synthetic peptides derived from the tick OsDef2 defensin. Journal of Peptide Science 28, 1-12 (e3383). https://doi.org/10.1002/psc.3383

2. ISMAIL NA, ODENDAAL C, SEREM JC, STRÖMSTEDT AA, BESTER MJ, SAYED Y, NEITZ AWH, & GASPAR ARM (2019). Antimicrobial function of short amidated peptide fragments from the tick derived OsDef2 defensin. Journal of Peptide Science 25, 1-9 (e3223). https://doi.org/10.1002/psc.3223

3. IBRAHIM MA, BESTER MJ, NEITZ AWH & GASPAR ARM (2019). Multiple antidiabetic effects of three α-glucosidase inhibitory peptides, PFP, YPI and YPG: Dipeptidyl-IV inhibition, suppression of lipid accumulation in differentiated 3T3-L1 adipocytes and scavenging activity on methylglyoxal. International Journal of Biological Macromolecules 122, 104-114. https://doi.org/10.1016/j.ijbiomac.2018.10.152

4. IBRAHIM MA, BESTER MJ, NEITZ AWH & GASPAR ARM (2018). Rational design of novel α-glucosidase inhibitory peptides and in vitro evaluation of promising candidates. Biomedicine and Pharmacotherapy 107, 234-242. https://doi.org/10.1016/j.biopha.2018.07.163

5. TAUTE H, BESTER MJ, NEITZ AWH & GASPAR ARM (2015). Investigation into the mechanism of action of the antimicrobial peptides Os and Os-C derived from a tick defensin. Peptides 71, 179-187. https://doi.org/10.1016/j.peptides.2015.07.017