Address: School of Chemistry, University of Melbourne, Parkville, VIC, 3010 Australia
Room: 212 – East Wing (Bld 154)
T: +61 8344 7985
Fluorescence investigations into the interactions of antimicrobial peptides with model & living cellular membranes
Antimicrobial resistance remains a serious global health issue, with an increasing prevalence of multi-drug resistant bacteria throughout the biosphere. Antimicrobial peptides offer a promising therapeutic alternative to conventional antibiotics, which act by directly permeating and disrupting bacterial cell membranes at relatively very low micromolar (μM) concentrations. Much contention persists surrounding the precise mechanism of action responsible for cell death, even for a given peptide. Numerous sources of influence, such as the presence of salts, sugars, pH, and, perhaps most importantly, membrane lipid composition, can all alter the observed behavioural outcome of peptides, complicating our mechanistic understanding of these compounds.
This work makes use of fluorescence imaging techniques; namely, frequency-domain fluorescence lifetime imaging, and Structured Illumination Microscopies; to monitor the evolution of peptide-membrane interactions in both artificial and living cell membranes. A model lytic peptide, Melittin P14K Alexa Fluor 430, based off the main component of European Honeybee (Apis mellifera) venom, has been well-characterised and shares similar activity to the native form. Changes in the peptide’s fluorescence response during interaction are monitored as a function of both concentration and time in order to gather mechanistic information regarding its behaviour with both giant vesicles and gram-negative bacteria. It is hoped a more complete understanding of this peptide will be gained as a result, as well as the potential implications with other systems,
This work is being performed in collaboration with the Melbourne Dental School, the ithree Institute at the University of Technology Sydney, the Walter & Eliza Hall Institute, and Swinburne University of Technology.