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 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. Ausführliche Beschreibung

Gespeichert in:

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

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2019

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

Übergeordnetes Werk:	In: mBio - American Society for Microbiology, 2010, 10(2019), 1
Übergeordnetes Werk:	volume:10 ; year:2019 ; number:1

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1128/mBio.02056-18

Katalog-ID:	DOAJ070877408

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allfields	10.1128/mBio.02056-18 doi (DE-627)DOAJ070877408 (DE-599)DOAJ9d970be129be462eb8daae5917e68e67 DE-627 ger DE-627 rakwb eng QR1-502 Jhih-Hang Jiang verfasserin aut Identification of Novel <italic toggle="yes"<Acinetobacter baumannii</italic< Host Fatty Acid Stress Adaptation Strategies 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. AdeIJK antimicrobial host lipids RND efflux β-oxidation free fatty acids lipidomics Microbiology Karl A. Hassan verfasserin aut Stephanie L. Begg verfasserin aut Thusitha W. T. Rupasinghe verfasserin aut Varsha Naidu verfasserin aut Victoria G. Pederick verfasserin aut Marjan Khorvash verfasserin aut Jonathan J. Whittall verfasserin aut James C. Paton verfasserin aut Ian T. Paulsen verfasserin aut Christopher A. McDevitt verfasserin aut Anton Y. Peleg verfasserin aut Bart A. Eijkelkamp verfasserin aut In mBio American Society for Microbiology, 2010 10(2019), 1 (DE-627)627613543 (DE-600)2557172-2 21507511 nnns volume:10 year:2019 number:1 https://doi.org/10.1128/mBio.02056-18 kostenfrei https://doaj.org/article/9d970be129be462eb8daae5917e68e67 kostenfrei https://journals.asm.org/doi/10.1128/mBio.02056-18 kostenfrei https://doaj.org/toc/2150-7511 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2019 1
spelling	10.1128/mBio.02056-18 doi (DE-627)DOAJ070877408 (DE-599)DOAJ9d970be129be462eb8daae5917e68e67 DE-627 ger DE-627 rakwb eng QR1-502 Jhih-Hang Jiang verfasserin aut Identification of Novel <italic toggle="yes"<Acinetobacter baumannii</italic< Host Fatty Acid Stress Adaptation Strategies 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. AdeIJK antimicrobial host lipids RND efflux β-oxidation free fatty acids lipidomics Microbiology Karl A. Hassan verfasserin aut Stephanie L. Begg verfasserin aut Thusitha W. T. Rupasinghe verfasserin aut Varsha Naidu verfasserin aut Victoria G. Pederick verfasserin aut Marjan Khorvash verfasserin aut Jonathan J. Whittall verfasserin aut James C. Paton verfasserin aut Ian T. Paulsen verfasserin aut Christopher A. McDevitt verfasserin aut Anton Y. Peleg verfasserin aut Bart A. Eijkelkamp verfasserin aut In mBio American Society for Microbiology, 2010 10(2019), 1 (DE-627)627613543 (DE-600)2557172-2 21507511 nnns volume:10 year:2019 number:1 https://doi.org/10.1128/mBio.02056-18 kostenfrei https://doaj.org/article/9d970be129be462eb8daae5917e68e67 kostenfrei https://journals.asm.org/doi/10.1128/mBio.02056-18 kostenfrei https://doaj.org/toc/2150-7511 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2019 1
allfields_unstemmed	10.1128/mBio.02056-18 doi (DE-627)DOAJ070877408 (DE-599)DOAJ9d970be129be462eb8daae5917e68e67 DE-627 ger DE-627 rakwb eng QR1-502 Jhih-Hang Jiang verfasserin aut Identification of Novel <italic toggle="yes"<Acinetobacter baumannii</italic< Host Fatty Acid Stress Adaptation Strategies 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. AdeIJK antimicrobial host lipids RND efflux β-oxidation free fatty acids lipidomics Microbiology Karl A. Hassan verfasserin aut Stephanie L. Begg verfasserin aut Thusitha W. T. Rupasinghe verfasserin aut Varsha Naidu verfasserin aut Victoria G. Pederick verfasserin aut Marjan Khorvash verfasserin aut Jonathan J. Whittall verfasserin aut James C. Paton verfasserin aut Ian T. Paulsen verfasserin aut Christopher A. McDevitt verfasserin aut Anton Y. Peleg verfasserin aut Bart A. Eijkelkamp verfasserin aut In mBio American Society for Microbiology, 2010 10(2019), 1 (DE-627)627613543 (DE-600)2557172-2 21507511 nnns volume:10 year:2019 number:1 https://doi.org/10.1128/mBio.02056-18 kostenfrei https://doaj.org/article/9d970be129be462eb8daae5917e68e67 kostenfrei https://journals.asm.org/doi/10.1128/mBio.02056-18 kostenfrei https://doaj.org/toc/2150-7511 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2019 1
allfieldsGer	10.1128/mBio.02056-18 doi (DE-627)DOAJ070877408 (DE-599)DOAJ9d970be129be462eb8daae5917e68e67 DE-627 ger DE-627 rakwb eng QR1-502 Jhih-Hang Jiang verfasserin aut Identification of Novel <italic toggle="yes"<Acinetobacter baumannii</italic< Host Fatty Acid Stress Adaptation Strategies 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. AdeIJK antimicrobial host lipids RND efflux β-oxidation free fatty acids lipidomics Microbiology Karl A. Hassan verfasserin aut Stephanie L. Begg verfasserin aut Thusitha W. T. Rupasinghe verfasserin aut Varsha Naidu verfasserin aut Victoria G. Pederick verfasserin aut Marjan Khorvash verfasserin aut Jonathan J. Whittall verfasserin aut James C. Paton verfasserin aut Ian T. Paulsen verfasserin aut Christopher A. McDevitt verfasserin aut Anton Y. Peleg verfasserin aut Bart A. Eijkelkamp verfasserin aut In mBio American Society for Microbiology, 2010 10(2019), 1 (DE-627)627613543 (DE-600)2557172-2 21507511 nnns volume:10 year:2019 number:1 https://doi.org/10.1128/mBio.02056-18 kostenfrei https://doaj.org/article/9d970be129be462eb8daae5917e68e67 kostenfrei https://journals.asm.org/doi/10.1128/mBio.02056-18 kostenfrei https://doaj.org/toc/2150-7511 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2019 1
allfieldsSound	10.1128/mBio.02056-18 doi (DE-627)DOAJ070877408 (DE-599)DOAJ9d970be129be462eb8daae5917e68e67 DE-627 ger DE-627 rakwb eng QR1-502 Jhih-Hang Jiang verfasserin aut Identification of Novel <italic toggle="yes"<Acinetobacter baumannii</italic< Host Fatty Acid Stress Adaptation Strategies 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. AdeIJK antimicrobial host lipids RND efflux β-oxidation free fatty acids lipidomics Microbiology Karl A. Hassan verfasserin aut Stephanie L. Begg verfasserin aut Thusitha W. T. Rupasinghe verfasserin aut Varsha Naidu verfasserin aut Victoria G. Pederick verfasserin aut Marjan Khorvash verfasserin aut Jonathan J. Whittall verfasserin aut James C. Paton verfasserin aut Ian T. Paulsen verfasserin aut Christopher A. McDevitt verfasserin aut Anton Y. Peleg verfasserin aut Bart A. Eijkelkamp verfasserin aut In mBio American Society for Microbiology, 2010 10(2019), 1 (DE-627)627613543 (DE-600)2557172-2 21507511 nnns volume:10 year:2019 number:1 https://doi.org/10.1128/mBio.02056-18 kostenfrei https://doaj.org/article/9d970be129be462eb8daae5917e68e67 kostenfrei https://journals.asm.org/doi/10.1128/mBio.02056-18 kostenfrei https://doaj.org/toc/2150-7511 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2019 1
language	English
source	In mBio 10(2019), 1 volume:10 year:2019 number:1
sourceStr	In mBio 10(2019), 1 volume:10 year:2019 number:1
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	AdeIJK antimicrobial host lipids RND efflux β-oxidation free fatty acids lipidomics Microbiology
isfreeaccess_bool	true
container_title	mBio
authorswithroles_txt_mv	Jhih-Hang Jiang @@aut@@ Karl A. Hassan @@aut@@ Stephanie L. Begg @@aut@@ Thusitha W. T. Rupasinghe @@aut@@ Varsha Naidu @@aut@@ Victoria G. Pederick @@aut@@ Marjan Khorvash @@aut@@ Jonathan J. Whittall @@aut@@ James C. Paton @@aut@@ Ian T. Paulsen @@aut@@ Christopher A. McDevitt @@aut@@ Anton Y. Peleg @@aut@@ Bart A. Eijkelkamp @@aut@@
publishDateDaySort_date	2019-01-01T00:00:00Z
hierarchy_top_id	627613543
id	DOAJ070877408
language_de	englisch
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callnumber-first	Q - Science
author	Jhih-Hang Jiang
spellingShingle	Jhih-Hang Jiang misc QR1-502 misc AdeIJK misc antimicrobial host lipids misc RND efflux misc β-oxidation misc free fatty acids misc lipidomics misc Microbiology Identification of Novel <italic toggle="yes"<Acinetobacter baumannii</italic< Host Fatty Acid Stress Adaptation Strategies
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topic_title	QR1-502 Identification of Novel <italic toggle="yes"<Acinetobacter baumannii</italic< Host Fatty Acid Stress Adaptation Strategies AdeIJK antimicrobial host lipids RND efflux β-oxidation free fatty acids lipidomics
topic	misc QR1-502 misc AdeIJK misc antimicrobial host lipids misc RND efflux misc β-oxidation misc free fatty acids misc lipidomics misc Microbiology
topic_unstemmed	misc QR1-502 misc AdeIJK misc antimicrobial host lipids misc RND efflux misc β-oxidation misc free fatty acids misc lipidomics misc Microbiology
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title	Identification of Novel <italic toggle="yes"<Acinetobacter baumannii</italic< Host Fatty Acid Stress Adaptation Strategies
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title_full	Identification of Novel <italic toggle="yes"<Acinetobacter baumannii</italic< Host Fatty Acid Stress Adaptation Strategies
author_sort	Jhih-Hang Jiang
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author_browse	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
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title_sort	identification of novel <italic toggle="yes"<acinetobacter baumannii</italic< host fatty acid stress adaptation strategies
callnumber	QR1-502
title_auth	Identification of Novel <italic toggle="yes"<Acinetobacter baumannii</italic< Host Fatty Acid Stress Adaptation Strategies
abstract	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.
abstractGer	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.
abstract_unstemmed	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.
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title_short	Identification of Novel <italic toggle="yes"<Acinetobacter baumannii</italic< Host Fatty Acid Stress Adaptation Strategies
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Identification of Novel <italic toggle="yes"<Acinetobacter baumannii</italic< Host Fatty Acid Stress Adaptation Strategies

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