Identification of Novel <italic toggle="yes">Acinetobacter baumannii</italic> Host Fatty Acid Stress Adaptation Strategies

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 ar...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	AdeIJK antimicrobial host lipids RND efflux β-oxidation free fatty acids lipidomics Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/9d970be129be462eb8daae5917e68e67
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spelling	oai:doaj.org-article:9d970be129be462eb8daae5917e68e672021-11-15T15:55:14ZIdentification of Novel <italic toggle="yes">Acinetobacter baumannii</italic> Host Fatty Acid Stress Adaptation Strategies10.1128/mBio.02056-182150-7511https://doaj.org/article/9d970be129be462eb8daae5917e68e672019-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02056-18https://doaj.org/toc/2150-7511ABSTRACT 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.Jhih-Hang JiangKarl A. HassanStephanie L. BeggThusitha W. T. RupasingheVarsha NaiduVictoria G. PederickMarjan KhorvashJonathan J. WhittallJames C. PatonIan T. PaulsenChristopher A. McDevittAnton Y. PelegBart A. EijkelkampAmerican Society for MicrobiologyarticleAdeIJKantimicrobial host lipidsRND effluxβ-oxidationfree fatty acidslipidomicsMicrobiologyQR1-502ENmBio, Vol 10, Iss 1 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	AdeIJK antimicrobial host lipids RND efflux β-oxidation free fatty acids lipidomics Microbiology QR1-502
spellingShingle	AdeIJK antimicrobial host lipids RND efflux β-oxidation free fatty acids lipidomics Microbiology QR1-502 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 Identification of Novel <italic toggle="yes">Acinetobacter baumannii</italic> Host Fatty Acid Stress Adaptation Strategies
description	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.
format	article
author	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
author_facet	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
author_sort	Jhih-Hang Jiang
title	Identification of Novel <italic toggle="yes">Acinetobacter baumannii</italic> Host Fatty Acid Stress Adaptation Strategies
title_short	Identification of Novel <italic toggle="yes">Acinetobacter baumannii</italic> Host Fatty Acid Stress Adaptation Strategies
title_full	Identification of Novel <italic toggle="yes">Acinetobacter baumannii</italic> Host Fatty Acid Stress Adaptation Strategies
title_fullStr	Identification of Novel <italic toggle="yes">Acinetobacter baumannii</italic> Host Fatty Acid Stress Adaptation Strategies
title_full_unstemmed	Identification of Novel <italic toggle="yes">Acinetobacter baumannii</italic> Host Fatty Acid Stress Adaptation Strategies
title_sort	identification of novel <italic toggle="yes">acinetobacter baumannii</italic> host fatty acid stress adaptation strategies
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/9d970be129be462eb8daae5917e68e67
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Identification of Novel <italic toggle="yes">Acinetobacter baumannii</italic> Host Fatty Acid Stress Adaptation Strategies

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