The Eijkelkamp Lab focusses on bacterial membrane biosynthesis and the transport systems that play key roles in the efflux of fatty acids and metal ions during stress. Through dietary supplementation of fatty acids (DHA or AA) or metals (zinc), we examine the possible adverse or beneficial impacts of these micronutrients upon bacterial pathogens during infection, using murine models. We also study how fatty acids and metal ions impact antibiotic efficacy, as significant synergy has been observed, but is not well understood. Overall, our aim is to understand the molecular basis of immune-mediated and antibiotic clearance of bacteria at the host-pathogen interface. This work will aid in the optimisation of dietary intervention strategies and antibiotic treatment in susceptible populations such as premature babies, the elderly and intensive-care patients.
We study these aspects of fatty acid and metal ion homeostasis in two major respiratory pathogens; Streptococcus pneumoniae, representing the leading bacterial pathogen in terms of annual mortality, and Acinetobacter baumannii as the world’s most problematic multidrug-resistant hospital pathogen.
Projects
The role of metal ion toxicity during infection
Our laboratory has identified and characterised the major zinc and copper transport systems in A. baumannii. Our current work focusses on the impact of simultaneous fluxes of distinct metal ions during infection, and how this affects bacterial pathogenesis. This is of primary interest as ratios of distinct metals are to be maintained within defined thresholds due to the synergistic antimicrobial activity of particular metal ion combinations, such as zinc and copper. To study the impact of metal ion fluxes in the complex environment as seen during infection, we have successfully established a murine model of zinc deficiency and subsequent zinc supplementation. This model also holds clinical relevance due to the global significance of human zinc deficiency, which affects nearly 2 billion people.
This project is conducted in collaboration with Prof Ian Paulsen (Macquarie University), Dr Amy Cain (Macquarie University) and Dr Karl Hassan (University of Newcastle).
The effects of antimicrobial fatty acids on bacterial physiology.
Host fatty acids hold dual roles during infection, modulating an immune response and directly killing invading bacteria. The primary antimicrobial host fatty acids are the omega-3 fatty acid docosahexaenoic acid and the omega-6 fatty acids arachidonic acid. The relative dietary intake of these fatty acids has shifted from 1:1, to a dramatic 20-fold relative increase in the consumption of omega-6 fatty acids. This has been associated with an increased risk of developing severe bacterial infections and omega-3 supplementation studies have shown a decrease in the incidence of respiratory infections. Our research has shown that the omega-3 fatty acid docosahexaenoic acid also exerts a greater antimicrobial activity upon major respiratory pathogens as compared to the omega-6 fatty acid arachidonic acid. Our current research examines how these host fatty acids exert their antimicrobial activity upon S. pneumoniae and A. baumannii, and which molecular mechanisms are employed by these pathogens to overcome their toxicity.
This project is conducted in collaboration with Prof Anton Peleg (Monash University), Prof Ian Paulsen (Macquarie University), A/Prof Mega O’Mara (Australian National University) and Dr Claudia Trappetti (University of Adelaide).