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dc.contributor.authorJakovljev, Aleksandra
dc.contributor.authorAfset, Jan Egil
dc.contributor.authorHaugum, Kjersti
dc.contributor.authorSteinum, Harald Otto
dc.contributor.authorRønning, Torunn Gresdal
dc.contributor.authorSamuelsen, Ørjan
dc.contributor.authorÅs, Christina Gabrielsen
dc.date.accessioned2022-11-17T08:56:35Z
dc.date.available2022-11-17T08:56:35Z
dc.date.issued2022-07-08
dc.description.abstractIntroduction<p> <p>Thymine auxotrophic in vitro mutants of Escherichia coli were first reported in the mid-20th century. Later, thymine-dependent clinical strains of E. coli as well as other Enterobacterales, Enterococcus faecalis and Staphylococcus aureus have been recognized as the cause of persistent and recurrent infections. <p>Objectives <p>The aim of this study was to characterize the phenotype and investigate the molecular basis of thymine auxotrophy in ten E. coli isolates obtained at different time points from a patient with recurrent bloodstream infection (BSI) due to a chronic aortic graft infection treated with Trimethoprim/sulfamethoxazole (TMP-SMX). <p>Methods <p>Clinical data was obtained from hospital records. Growth characterization and antimicrobial susceptibility testing to TMP-SMX was performed on M9 agar and in MH broth with different thymine concentrations (0.5, 2, 5, 10 and 20 μg/mL), on Mueller-Hinton (MH) and blood agar. Whole genome sequencing (WGS) was performed on all E. coli isolates. <p>Results <p>E. coli were isolated from ten consecutive BSI episodes from a patient with chronic aortic graft infection. Six of these isolates were resistant to TMP-SMX when assayed on blood agar. Growth experiments with added thymine confirmed that these isolates were thyminedependent (thy-), and revealed growth defects (slower growth rate and smaller colony size in these isolates relative to thy+ isolates (n = 4). WGS indicated that all isolates were of the same clonal lineage of sequence type 7358. Genomic analysis revealed a G172C substitution in thyA in all TMP-SMX resistant isolates, while mutations affecting genes involved in the deoxyribose salvage pathway (deoB and deoC) were identified in eight isolates. <p>Conclusion <p>This case highlights the risk of resistance development to TMP-SMX, especially for longterm treatment, and the possible pitfalls in detection of growth-deficient subpopulations from chronic infections, which could lead to treatment failure.en_US
dc.identifier.citationJakovljev, Afset, Haugum, Steinum, Rønning, Samuelsen, Ås. Phenotypic and genotypic characterisation of thymine auxotrophy in Escherichia coli isolated from a patient with recurrent bloodstream infection. PLOS ONE. 2022;17(7)en_US
dc.identifier.cristinIDFRIDAID 2058205
dc.identifier.doi10.1371/journal.pone.0270256
dc.identifier.issn1932-6203
dc.identifier.urihttps://hdl.handle.net/10037/27395
dc.language.isoengen_US
dc.publisherPLOSen_US
dc.relation.journalPLOS ONE
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2022 The Author(s)en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0en_US
dc.rightsAttribution 4.0 International (CC BY 4.0)en_US
dc.titlePhenotypic and genotypic characterisation of thymine auxotrophy in Escherichia coli isolated from a patient with recurrent bloodstream infectionen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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Attribution 4.0 International (CC BY 4.0)
Except where otherwise noted, this item's license is described as Attribution 4.0 International (CC BY 4.0)