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dc.contributor.authorSumabe, Balagra Kasim
dc.contributor.authorRæder, Synnøve Brandt
dc.contributor.authorRøst, Lisa M.
dc.contributor.authorSharma, Animesh
dc.contributor.authorDonkor, Eric S.
dc.contributor.authorMosi, Lydia
dc.contributor.authorDuodu, Samuel
dc.contributor.authorBruheim, Per
dc.contributor.authorOtterlei, Marit
dc.date.accessioned2023-01-22T16:12:41Z
dc.date.available2023-01-22T16:12:41Z
dc.date.created2021-06-08T13:34:26Z
dc.date.issued2021
dc.identifier.citationBiomolecules. 2021, 11 (6), .en_US
dc.identifier.issn2218-273X
dc.identifier.urihttps://hdl.handle.net/11250/3045080
dc.description.abstractDrugs targeting DNA and RNA in mammalian cells or viruses can also affect bacteria present in the host and thereby induce the bacterial SOS system. This has the potential to increase mutagenesis and the development of antimicrobial resistance (AMR). Here, we have examined nucleoside analogues (NAs) commonly used in anti-viral and anti-cancer therapies for potential effects on mutagenesis in Escherichia coli, using the rifampicin mutagenicity assay. To further explore the mode of action of the NAs, we applied E. coli deletion mutants, a peptide inhibiting Pol V (APIM-peptide) and metabolome and proteome analyses. Five out of the thirteen NAs examined, including three nucleoside reverse transcriptase inhibitors (NRTIs) and two anti-cancer drugs, increased the mutation frequency in E. coli by more than 25-fold at doses that were within reported plasma concentration range (Pl.CR), but that did not affect bacterial growth. We show that the SOS response is induced and that the increase in mutation frequency is mediated by the TLS polymerase Pol V. Quantitative mass spectrometry-based metabolite profiling did not reveal large changes in nucleoside phosphate or other central carbon metabolite pools, which suggests that the SOS induction is an effect of increased replicative stress. Our results suggest that NAs/NRTIs can contribute to the development of AMR and that drugs inhibiting Pol V can reverse this mutagenesis.en_US
dc.language.isoengen_US
dc.relation.urihttps://www.ebi.ac.uk/pride/archive/projects/PXD025370
dc.rightsNavngivelse 4.0 Internasjonal*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/deed.no*
dc.titleNucleoside Analogues Are Potent Inducers of Pol V-mediated Mutagenesisen_US
dc.title.alternativeNucleoside Analogues Are Potent Inducers of Pol V-mediated Mutagenesisen_US
dc.typeJournal articleen_US
dc.typePeer revieweden_US
dc.description.versionpublishedVersionen_US
dc.source.pagenumber13en_US
dc.source.volume11en_US
dc.source.journalBiomoleculesen_US
dc.source.issue6en_US
dc.identifier.doi10.3390/biom11060843
dc.identifier.cristin1914539
dc.relation.projectSigma2: NS9036Ken_US
dc.relation.projectSigma2: NN9036Ken_US
cristin.ispublishedtrue
cristin.fulltextoriginal
cristin.qualitycode1


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