Arachidonic acid stress impacts pneumococcal fatty acid homeostasis

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dc.contributor.authorEijkelkamp, B.
dc.contributor.authorBegg, S.
dc.contributor.authorPederick, V.
dc.contributor.authorTrapetti, C.
dc.contributor.authorGregory, M.
dc.contributor.authorWhittall, J.
dc.contributor.authorPaton, J.
dc.contributor.authorMcDevitt, C.
dc.date.issued2018
dc.descriptionPublished: 11 May 2018
dc.description.abstractFree fatty acids hold dual roles during infection, serving to modulate the host immune response while also functioning directly as antimicrobials. Of particular importance are the long chain polyunsaturated fatty acids, which are not commonly found in bacterial organisms, that have been proposed to have antibacterial roles. Arachidonic acid (AA) is a highly abundant long chain polyunsaturated fatty acid and we examined its effect upon Streptococcus pneumoniae. Here, we observed that in a murine model of S. pneumoniae infection the concentration of AA significantly increases in the blood. The impact of AA stress upon the pathogen was then assessed by a combination of biochemical, biophysical and microbiological assays. In vitro bacterial growth and intra-macrophage survival assays revealed that AA has detrimental effects on pneumococcal fitness. Subsequent analyses demonstrated that AA exerts antimicrobial activity via insertion into the pneumococcal membrane, although this did not increase the susceptibility of the bacterium to antibiotic, oxidative or metal ion stress. Transcriptomic profiling showed that AA treatment also resulted in a dramatic down-regulation of the genes involved in fatty acid biosynthesis, in addition to impacts on other metabolic processes, such as carbon-source utilization. Hence, these data reveal that AA has two distinct mechanisms of perturbing the pneumococcal membrane composition. Collectively, this work provides a molecular basis for the antimicrobial contribution of AA to combat pneumococcal infections.
dc.description.statementofresponsibilityBart A. Eijkelkamp, Stephanie L. Begg, Victoria G. Pederick, Claudia Trapetti, Melissa K. Gregory, Jonathan J. Whittall, James C. Paton and Christopher A. McDevitt
dc.identifier.citationFrontiers in Microbiology, 2018; 9(MAY):813-1-813-12
dc.identifier.doi10.3389/fmicb.2018.00813
dc.identifier.issn1664-302X
dc.identifier.issn1664-302X
dc.identifier.orcidEijkelkamp, B. [0000-0003-0179-8977]
dc.identifier.orcidBegg, S. [0000-0002-7298-9335]
dc.identifier.orcidGregory, M. [0000-0002-6538-6720]
dc.identifier.orcidPaton, J. [0000-0001-9807-5278]
dc.identifier.orcidMcDevitt, C. [0000-0003-1596-4841]
dc.identifier.urihttp://hdl.handle.net/2440/112399
dc.language.isoen
dc.publisherFrontiers Media
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1080784
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1122582
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1071659
dc.relation.granthttp://purl.org/au-research/grants/arc/DP150104515
dc.relation.granthttp://purl.org/au-research/grants/arc/DP170102102
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1142695
dc.relation.granthttp://purl.org/au-research/grants/arc/FT170100006
dc.rightsCopyright © 2018 Eijkelkamp, Begg, Pederick, Trapetti, Gregory,Whittall, Paton and McDevitt. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
dc.source.urihttps://doi.org/10.3389/fmicb.2018.00813
dc.subjectHost lipids; free fatty acids; membrane fluidity; macrophages; antibacterial fatty acids; FASII
dc.titleArachidonic acid stress impacts pneumococcal fatty acid homeostasis
dc.typeJournal article
pubs.publication-statusPublished

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