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dc.contributor.authorPedersen, Torunn Annie
dc.contributor.authorTellevik, Marit Gjerde
dc.contributor.authorKommedal, Øyvind
dc.contributor.authorLindemann, Paul Christoffer
dc.contributor.authorMoyo, Sabrina John
dc.contributor.authorJanice, Jessin
dc.contributor.authorBlomberg, Bjørn
dc.contributor.authorSamuelsen, Ørjan
dc.contributor.authorLangeland, Nina
dc.date.accessioned2020-09-22T07:27:57Z
dc.date.available2020-09-22T07:27:57Z
dc.date.issued2020-07-15
dc.description.abstractIncreased knowledge about the role of horizontal gene transfer is key to improve our understanding of the spread of antimicrobial resistance (AMR) in human populations. We therefore studied the dissemination of the <i>bla</i><sub>CTX-M-15</sub> extended-spectrum-β-lactamase (ESBL) gene in <i>Klebsiella pneumoniae</i> isolates obtained from stool samples from hospitalized children and healthy controls below 2 years of age in Dar es Salaam, Tanzania, from August 2010 to July 2011. We performed Illumina whole-genome sequencing (WGS) to characterize resistance genes, multilocus sequence type (MLST), plasmid incompatibility group (Inc), and plasmid MLST of 128 isolates of <i>K. pneumoniae</i> with <i>bla</i><sub>CTX-M-15</sub> recovered from both healthy and hospitalized children. We assessed the phylogenetic relationship using single nucleotide polymorphism (SNP)-based analysis and resolved the sequences of five reference plasmids by Oxford Nanopore technology to investigate plasmid dissemination. The WGS analyses revealed the presence of a <i>bla</i><sub>CTX-M-15</sub>-positive IncFII<sub>K5</sub>/IncR plasmid with a highly conserved backbone in 70% (90/128) of the isolates. This plasmid, harboring genes encoding resistance to most β-lactams, aminoglycosides, trimethoprim-sulfamethoxazole, and chloramphenicol, was present in phylogenetically very diverse <i>K. pneumoniae</i> strains (48 different MLSTs) carried by both hospitalized and healthy children. Our data strongly suggest widespread horizontal transfer of this ESBL-carrying plasmid both in hospitals and in the general population.<p><p> IMPORTANCE - Horizontal spread of plasmids carrying multiple resistance genes is considered an important mechanism behind the global health problem caused by multidrug-resistant bacteria. Nevertheless, knowledge about spread of plasmids in a community is limited. Our detailed molecular analyses of <i>K. pneumoniae</i> isolated from hospitalized and healthy children in Tanzania disclosed an epidemic spread of a resistance plasmid. In this study population, we revealed horizontal plasmid transfer among <i>K. pneumoniae</i> as the key factor for dissemination of ESBLs. Traditional outbreak investigation and surveillance focus on the spread of bacterial clones, and short-read sequencing can result in erroneous plasmid composition. Our approach using long-read sequencing reveals horizontal gene transfer of antimicrobial resistance, and therefore has a potential impact on outbreak investigations and approaches to limit spread of AMR.en_US
dc.identifier.citationPedersen, Tellevik, Kommedal, Lindemann, Moyo, James Peter, Blomberg, Samuelsen, Langeland. Horizontal plasmid transfer among klebsiella pneumoniae isolates is the key factor for dissemination of extended-spectrum β-lactamases among children in Tanzania. mSphere. 2020;5:e00428-20(4):1-13en_US
dc.identifier.cristinIDFRIDAID 1827810
dc.identifier.doi10.1128/mSphere.00428-20
dc.identifier.issn2379-5042
dc.identifier.urihttps://hdl.handle.net/10037/19450
dc.language.isoengen_US
dc.publisherAmerican Society for Microbiologyen_US
dc.relation.journalmSphere
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2020 The Author(s)en_US
dc.subjectVDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710en_US
dc.subjectVDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710en_US
dc.titleHorizontal plasmid transfer among klebsiella pneumoniae isolates is the key factor for dissemination of extended-spectrum β-lactamases among children in Tanzaniaen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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