Oral Presentation BACPATH 2019

Antimicrobial fatty acids impact membrane biology and antibiotic resistance in Acinetobacter baumannii (#51)

Jhih-Hang Jiang 1 , Felise G Adams 2 , Maoge Zang 2 , Marjan Khorvash 2 , Stephanie L Begg 3 , Thusitha WT Rupasinghe 4 , Varsha Naidu 5 , Victoria G Pederick 2 , Jonathan J Whittall 2 6 , James C Paton 2 , Ian T Paulsen 5 , Karl A Hassan 7 , Christopher A McDevitt 3 , Anton Y Peleg 1 8 , Bart A Eijkelkamp 2
  1. Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Microbiology, Monash University, Clayton, VIC, Australia
  2. Research Centre for Infectious Diseases, University of Adelaide, Adelaide, SA, Australia
  3. The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC, Australia
  4. Metabolomics Australia, School of BioSciences, University of Melbourne, Melbourne, VIC, Australia
  5. Department of Chemistry and Biomolecular Sciences, Macquarie University, Sydney, NSW, Australia
  6. School of Pharmacy and Medical Sciences, Sansom Institute for Health Research, University of South Australia, Adelaide, SA, Australia
  7. School of Environmental and Life Sciences, University of Newcastle, Newcastle, NSW, Australia
  8. Department of Infectious Diseases, The Alfred Hospital and Central Clinical School, Monash University, Melbourne, VIC, Australia

Free fatty acids hold important immune-modulatory roles during infection. However, the host’s long chain polyunsaturated fatty acids, not commonly found in the membranes of bacterial pathogens, also have significant broad-spectrum antibacterial potential. Of these, the omega-6 fatty acid arachidonic acid (AA) and the omega-3 fatty acid decosahexaenoic acid (DHA) are highly abundant, hence, we investigated their effects on Acinetobacter baumannii. Our analyses reveal that AA and DHA readily incorporate into the A. baumannii membrane and impact membrane integrity. Importantly, our analyses also reveal a role for environmental fatty acids in antibiotic susceptibly and the development of antibiotic resistance in A. baumannii. Through transcriptional profiling and mutant analyses, we identified multiple lipid homeostasis mechanisms that play a role in AA and DHA resistance, including the b-oxidation pathway, the AdeIJK RND efflux system and a DesB-like desaturase. This is the first study to examine the antimicrobial effects of host fatty acids on A. baumannii, and highlights the potential of AA and DHA to protect against A. baumannii infections. Further, the novel role for fatty acids in antimicrobial resistance provides insights into the complex interplay between host factors and anti-A. baumannii therapy.