Identification of Novel Acinetobacter baumannii Host Fatty Acid Stress Adaptation Strategies

Jhih Hang Jiang, Karl A. Hassan, Stephanie L. Begg, Thusitha W.T. Rupasinghe, Varsha Naidu, Victoria G. Pederick, Marjan Khorvash, Jonathan J. Whittall, James C. Paton, Ian T. Paulsen, Christopher A. McDevitt, Anton Y. Peleg, Bart A. Eijkelkamp

Research output: Contribution to journalArticleResearchpeer-review

Abstract

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 the multidrug-resistant human pathogen Acinetobacter baumannii Our analyses reveal that AA and DHA incorporate into the A. baumannii bacterial membrane and impact bacterial fitness and membrane integrity, with DHA having a more pronounced effect. Through transcriptional profiling and mutant analyses, we show that the A. baumannii β-oxidation pathway plays a protective role against AA and DHA, by limiting their incorporation into the phospholipids of the bacterial membrane. Furthermore, our study identified a second bacterial membrane protection system mediated by the AdeIJK efflux system, which modulates the lipid content of the membrane via direct efflux of lipids other than AA and DHA, thereby providing a novel function for this major efflux system in A. baumannii 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.IMPORTANCE 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.

Original languageEnglish
Article numbere02056-18
Number of pages6
JournalmBio
Volume10
Issue number1
DOIs
Publication statusPublished - 5 Feb 2019

Keywords

  • AdeIJK
  • antimicrobial host lipids
  • free fatty acids
  • lipidomics
  • RND efflux
  • β-oxidation

Cite this

Jiang, J. H., Hassan, K. A., Begg, S. L., Rupasinghe, T. W. T., Naidu, V., Pederick, V. G., ... Eijkelkamp, B. A. (2019). Identification of Novel Acinetobacter baumannii Host Fatty Acid Stress Adaptation Strategies. mBio, 10(1), [e02056-18]. https://doi.org/10.1128/mBio.02056-18
Jiang, Jhih Hang ; Hassan, Karl A. ; Begg, Stephanie L. ; Rupasinghe, Thusitha W.T. ; Naidu, Varsha ; Pederick, Victoria G. ; Khorvash, Marjan ; Whittall, Jonathan J. ; Paton, James C. ; Paulsen, Ian T. ; McDevitt, Christopher A. ; Peleg, Anton Y. ; Eijkelkamp, Bart A. / Identification of Novel Acinetobacter baumannii Host Fatty Acid Stress Adaptation Strategies. In: mBio. 2019 ; Vol. 10, No. 1.
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abstract = "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 the multidrug-resistant human pathogen Acinetobacter baumannii Our analyses reveal that AA and DHA incorporate into the A. baumannii bacterial membrane and impact bacterial fitness and membrane integrity, with DHA having a more pronounced effect. Through transcriptional profiling and mutant analyses, we show that the A. baumannii β-oxidation pathway plays a protective role against AA and DHA, by limiting their incorporation into the phospholipids of the bacterial membrane. Furthermore, our study identified a second bacterial membrane protection system mediated by the AdeIJK efflux system, which modulates the lipid content of the membrane via direct efflux of lipids other than AA and DHA, thereby providing a novel function for this major efflux system in A. baumannii 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.IMPORTANCE 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.",
keywords = "AdeIJK, antimicrobial host lipids, free fatty acids, lipidomics, RND efflux, β-oxidation",
author = "Jiang, {Jhih Hang} and Hassan, {Karl A.} and Begg, {Stephanie L.} and Rupasinghe, {Thusitha W.T.} and Varsha Naidu and Pederick, {Victoria G.} and Marjan Khorvash and Whittall, {Jonathan J.} and Paton, {James C.} and Paulsen, {Ian T.} and McDevitt, {Christopher A.} and Peleg, {Anton Y.} and Eijkelkamp, {Bart A.}",
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Jiang, JH, Hassan, KA, Begg, SL, Rupasinghe, TWT, Naidu, V, Pederick, VG, Khorvash, M, Whittall, JJ, Paton, JC, Paulsen, IT, McDevitt, CA, Peleg, AY & Eijkelkamp, BA 2019, 'Identification of Novel Acinetobacter baumannii Host Fatty Acid Stress Adaptation Strategies' mBio, vol. 10, no. 1, e02056-18. https://doi.org/10.1128/mBio.02056-18

Identification of Novel Acinetobacter baumannii Host Fatty Acid Stress Adaptation Strategies. / Jiang, Jhih Hang; Hassan, Karl A.; Begg, Stephanie L.; Rupasinghe, Thusitha W.T.; Naidu, Varsha; Pederick, Victoria G.; Khorvash, Marjan; Whittall, Jonathan J.; Paton, James C.; Paulsen, Ian T.; McDevitt, Christopher A.; Peleg, Anton Y.; Eijkelkamp, Bart A.

In: mBio, Vol. 10, No. 1, e02056-18, 05.02.2019.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Identification of Novel Acinetobacter baumannii Host Fatty Acid Stress Adaptation Strategies

AU - Jiang, Jhih Hang

AU - Hassan, Karl A.

AU - Begg, Stephanie L.

AU - Rupasinghe, Thusitha W.T.

AU - Naidu, Varsha

AU - Pederick, Victoria G.

AU - Khorvash, Marjan

AU - Whittall, Jonathan J.

AU - Paton, James C.

AU - Paulsen, Ian T.

AU - McDevitt, Christopher A.

AU - Peleg, Anton Y.

AU - Eijkelkamp, Bart A.

PY - 2019/2/5

Y1 - 2019/2/5

N2 - 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 the multidrug-resistant human pathogen Acinetobacter baumannii Our analyses reveal that AA and DHA incorporate into the A. baumannii bacterial membrane and impact bacterial fitness and membrane integrity, with DHA having a more pronounced effect. Through transcriptional profiling and mutant analyses, we show that the A. baumannii β-oxidation pathway plays a protective role against AA and DHA, by limiting their incorporation into the phospholipids of the bacterial membrane. Furthermore, our study identified a second bacterial membrane protection system mediated by the AdeIJK efflux system, which modulates the lipid content of the membrane via direct efflux of lipids other than AA and DHA, thereby providing a novel function for this major efflux system in A. baumannii 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.IMPORTANCE 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.

AB - 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 the multidrug-resistant human pathogen Acinetobacter baumannii Our analyses reveal that AA and DHA incorporate into the A. baumannii bacterial membrane and impact bacterial fitness and membrane integrity, with DHA having a more pronounced effect. Through transcriptional profiling and mutant analyses, we show that the A. baumannii β-oxidation pathway plays a protective role against AA and DHA, by limiting their incorporation into the phospholipids of the bacterial membrane. Furthermore, our study identified a second bacterial membrane protection system mediated by the AdeIJK efflux system, which modulates the lipid content of the membrane via direct efflux of lipids other than AA and DHA, thereby providing a novel function for this major efflux system in A. baumannii 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.IMPORTANCE 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.

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KW - free fatty acids

KW - lipidomics

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Jiang JH, Hassan KA, Begg SL, Rupasinghe TWT, Naidu V, Pederick VG et al. Identification of Novel Acinetobacter baumannii Host Fatty Acid Stress Adaptation Strategies. mBio. 2019 Feb 5;10(1). e02056-18. https://doi.org/10.1128/mBio.02056-18