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dc.contributor.authorSherrard, LJ
dc.contributor.authorWee, BA
dc.contributor.authorDuplancic, C
dc.contributor.authorRamsay, KA
dc.contributor.authorDave, KA
dc.contributor.authorBallard, E
dc.contributor.authorWainwright, CE
dc.contributor.authorGrimwood, K
dc.contributor.authorSidjabat, HE
dc.contributor.authorWhiley, DM
dc.contributor.authorBeatson, SA
dc.contributor.authorKidd, TJ
dc.contributor.authorBell, SC
dc.date.accessioned2021-04-13T02:20:58Z
dc.date.available2021-04-13T02:20:58Z
dc.date.issued2021
dc.identifier.issn1569-1993
dc.identifier.doi10.1016/j.jcf.2021.03.007
dc.identifier.urihttp://hdl.handle.net/10072/403682
dc.description.abstractBackground: Antimicrobial resistance in cystic fibrosis (CF) Pseudomonas aeruginosa airway infection is complex and often attributed to chromosomal mutations. How these mutations emerge in specific strains or whether particular gene mutations are clinically informative is unclear. This study focused on oprD, which encodes an outer membrane porin associated with carbapenem resistance when it is downregulated or inactivated. Aim: Determine how mutations in oprD emerge in two prevalent Australian shared CF strains of P. aeruginosa and their clinical relevance. Methods: The two most common shared CF strains in Queensland were investigated using whole genome sequencing and their oprD sequences and antimicrobial resistance phenotypes were established. P. aeruginosa mutants with the most common oprD variants were constructed and characterised. Clinical variables were compared between people with or without evidence of infection with strains harbouring these variants. Results: Frequently found nonsense mutations arising from a 1-base pair substitution in oprD evolved independently in three sub-lineages, and are likely major contributors to the reduced carbapenem susceptibility observed in the clinical isolates. Lower baseline FEV %predicted was identified as a risk factor for infection with a sub-lineage (odds ratio=0.97; 95% confidence interval 0.96-0.99; p<0.001). However, acquiring these sub-lineage strains did not confer an accelerated decline in FEV nor increase the risk of death/lung transplantation. Conclusions: Sub-lineages harbouring specific mutations in oprD have emerged and persisted in the shared strain populations. Infection with the sub-lineages was more likely in people with lower lung function, but this was not predictive of a worse clinical trajectory. 1 1
dc.description.peerreviewedYes
dc.languageeng
dc.publisherElsevier BV
dc.relation.ispartofjournalJournal of Cystic Fibrosis
dc.subject.fieldofresearchClinical Sciences
dc.subject.fieldofresearchcode1103
dc.subject.keywordsAntimicrobial resistance
dc.subject.keywordsClinical outcomes
dc.subject.keywordsCystci fibrosis
dc.subject.keywordsOPRD
dc.subject.keywordsPseudomonas aeruginosa
dc.titleEmergence and impact of oprD mutations in Pseudomonas aeruginosa strains in cystic fibrosis
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationSherrard, LJ; Wee, BA; Duplancic, C; Ramsay, KA; Dave, KA; Ballard, E; Wainwright, CE; Grimwood, K; Sidjabat, HE; Whiley, DM; Beatson, SA; Kidd, TJ; Bell, SC, Emergence and impact of oprD mutations in Pseudomonas aeruginosa strains in cystic fibrosis, Journal of Cystic Fibrosis, 2021
dcterms.dateAccepted2021-03-02
dcterms.licensehttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.date.updated2021-04-13T01:50:59Z
dc.description.versionAccepted Manuscript (AM)
gro.description.notepublicThis publication has been entered in Griffith Research Online as an advanced online version.
gro.rights.copyright© 2021 European Cystic Fibrosis Society. Published by Elsevier Ltd. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Licence (http://creativecommons.org/licenses/by-nc-nd/4.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, providing that the work is properly cited.
gro.hasfulltextFull Text
gro.griffith.authorGrimwood, Keith
gro.griffith.authorSidjabat, Hanna E.


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