Identification of Novel Acinetobacter baumannii Host Fatty Acid Stress Adaptation Strategies

Author:

Jiang Jhih-Hang1,Hassan Karl A.2,Begg Stephanie L.34,Rupasinghe Thusitha W. T.5,Naidu Varsha6,Pederick Victoria G.3,Khorvash Marjan3,Whittall Jonathan J.37,Paton James C.3,Paulsen Ian T.6,McDevitt Christopher A.4ORCID,Peleg Anton Y.18,Eijkelkamp Bart A.3ORCID

Affiliation:

1. Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Microbiology, Monash University, Clayton, Victoria, Australia

2. School of Environmental and Life Sciences, University of Newcastle, Callaghan, New South Wales, Australia

3. Research Centre for Infectious Diseases, School of Biological Sciences, University of Adelaide, Adelaide, South Australia, Australia

4. Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia

5. Metabolomics Australia, School of BioSciences, University of Melbourne, Melbourne, Victoria, Australia

6. Department of Chemistry and Biomolecular Sciences, Macquarie University, Sydney, New South Wales, Australia

7. School of Pharmacy and Medical Sciences, Sansom Institute for Health Research, University of South Australia, Adelaide, South Australia, Australia

8. Department of Infectious Diseases, The Alfred Hospital and Central Clinical School, Monash University, Melbourne, Victoria, Australia

Abstract

A shift in the Western diet since the industrial revolution has resulted in a dramatic increase in the consumption of omega-6 fatty acids, with a concurrent decrease in the consumption of omega-3 fatty acids. This decrease in omega-3 fatty acid consumption has been associated with significant disease burden, including increased susceptibility to infectious diseases. Here we provide evidence that DHA, an omega-3 fatty acid, has superior antimicrobial effects upon the highly drug-resistant pathogen Acinetobacter baumannii , thereby providing insights into one of the potential health benefits of omega-3 fatty acids. The identification and characterization of two novel bacterial membrane protective mechanisms against host fatty acids provide important insights into A. baumannii adaptation during disease. Furthermore, we describe a novel role for the major multidrug efflux system AdeIJK in A. baumannii membrane maintenance and lipid transport. This core function, beyond drug efflux, increases the appeal of AdeIJK as a therapeutic target.

Funder

University of Adelaide Beacon Fellowship

Department of Health | National Health and Medical Research Council

Department of Education and Training | Australian Research Council

Publisher

American Society for Microbiology

Subject

Virology,Microbiology

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