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dc.contributor.authorO'Brien, Thomas James
dc.contributor.authorFigueroa, Wendy
dc.contributor.authorWelch, Martin
dc.date.accessioned2022-06-29T19:43:22Z
dc.date.available2022-06-29T19:43:22Z
dc.date.issued2022-07
dc.date.submitted2021-09-24
dc.identifier.issn1751-7362
dc.identifier.others41396-022-01218-7
dc.identifier.other1218
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/338451
dc.descriptionFunder: Cystic Fibrosis Trust (CF); doi: https://doi.org/10.13039/501100000292
dc.descriptionFunder: British Lung Foundation (BLF); doi: https://doi.org/10.13039/501100000351
dc.description.abstractThe airways of people with cystic fibrosis (CF) often harbour diverse polymicrobial communities. These airway infections can be impossible to resolve through antibiotic intervention, even though isolates of the individual species present are susceptible to the treatment when tested in vitro. In this work, we investigate how polymicrobial cultures comprised of key CF-associated pathogens respond to challenge with species-specific antimicrobial agents; colistin (targets Pseudomonas aeruginosa), fusidic acid (targets Staphylococcus aureus), and fluconazole (targets Candida albicans). We found that growth in a polymicrobial environment protects the target microorganism (sometimes by several orders of magnitude) from the effect(s) of the antimicrobial agent. This decreased antimicrobial efficacy was found to have both non-heritable (physiological) and heritable (genetic) components. Whole-genome sequencing of the colistin-resistant P. aeruginosa isolates revealed single nucleotide polymorphisms and indels in genes encoding lipopolysaccharide (LPS) biosynthesis and/or pilus biogenesis, indicating that a previously undescribed colistin resistance mechanism was in operation. This was subsequently confirmed through further genetic analyses. Our findings indicate that the polymicrobial nature of the CF airways is likely to have a significant impact on the clinical response to antimicrobial therapy.
dc.languageen
dc.publisherSpringer Science and Business Media LLC
dc.subjectArticle
dc.subject/631/326/2565/107
dc.subject/631/326/22/1290
dc.subject/45/22
dc.subject/45/23
dc.subject/45/90
dc.subject/42/44
dc.subject/45
dc.subjectarticle
dc.titleDecreased efficacy of antimicrobial agents in a polymicrobial environment.
dc.typeArticle
dc.date.updated2022-06-29T19:43:21Z
prism.endingPage1704
prism.issueIdentifier7
prism.publicationNameISME J
prism.startingPage1694
prism.volume16
dc.identifier.doi10.17863/CAM.85864
dcterms.dateAccepted2022-02-21
rioxxterms.versionofrecord10.1038/s41396-022-01218-7
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidO'Brien, Thomas James [0000-0002-5529-331X]
dc.contributor.orcidFigueroa, Wendy [0000-0003-0882-5106]
dc.contributor.orcidWelch, Martin [0000-0003-3646-1733]
dc.identifier.eissn1751-7370
pubs.funder-project-idNational Centre for the Replacement Refinement and Reduction of Animals in Research (NC/P001564/1)
cam.issuedOnline2022-03-19


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