• Antimicrobial resistance acquisition via natural transformation: context is everything 

      Winter, Macaulay; Buckling, Angus; Harms, Klaus; Johnsen, Pål Jarle; Vos, Michiel (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-10-26)
      Natural transformation is a process where bacterial cells actively take up free DNA from the environment and recombine it into their genome or reconvert it into extra-chromosomal genetic elements. Although this mechanism is known to mediate the uptake of antibiotic resistance determinants in a range of human pathogens, its importance in the spread of antimicrobial resistance is not always appreciated. ...
    • Bacterial evolution on demand 

      Johnsen, Pål Jarle; Gama, João Alves; Harms, Klaus (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-04-06)
      Bacteria carry antibiotic resistant genes on movable sections of DNA that allow them to select the relevant genes on demand.
    • The chemotherapeutic drug methotrexate selects for antibiotic resistance 

      Gudmundsdottir, Jonina; Fredheim, Elizabeth G. Aarag; Koumans, Catharina I.M.; Hegstad, Joachim; Tang, Po-Cheng; Andersson, Dan I.; Samuelsen, Ørjan; Johnsen, Pål Jarle (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-12-11)
      Background: Understanding drivers of antibiotic resistance evolution is fundamental for designing optimal treatment strategies and interventions to reduce the spread of antibiotic resistance. Various cytotoxic drugs used in cancer chemotherapy have antibacterial properties, but how bacterial populations are affected by these selective pressures is unknown. Here we test the hypothesis that the widely ...
    • Conserved collateral antibiotic susceptibility networks in diverse clinical strains of Escherichia coli 

      Podnecky, Nicole L.; Aarag, Elizabeth; Kloos, Julia Maria; Sørum, Vidar; Primicerio, Raul; Roberts, Adam Paul; Rozen, Daniel E.; Samuelsen, Ørjan; Johnsen, Pål Jarle (Journal article; Tidsskriftartikkel; Peer reviewed, 2018-09-10)
      There is urgent need to develop novel treatment strategies to reduce antimicrobial resistance. Collateral sensitivity (CS), where resistance to one antimicrobial increases susceptibility to other drugs, might enable selection against resistance during treatment. However, the success of this approach would depend on the conservation of CS networks across genetically diverse bacterial strains. Here, ...
    • Costs and benefits of natural transformation in Acinetobacter baylyi 

      Hülter, Nils Fredrik; Sørum, Vidar; Borch-Pedersen, Kristina; Liljegren, Mikkel Meyn; Utnes, Ane; Primicerio, Raul; Harms, Klaus; Johnsen, Pål Jarle (Journal article; Tidsskriftartikkel; Peer reviewed, 2017-02-15)
      Background <br> Natural transformation enables acquisition of adaptive traits and drives genome evolution in prokaryotes. Yet, the selective forces responsible for the evolution and maintenance of natural transformation remain elusive since taken-up DNA has also been hypothesized to provide benefits such as nutrients or templates for DNA repair to individual cells. <br> Results <br> We investigated ...
    • Cryptic β-Lactamase Evolution Is Driven by Low β-Lactam Concentrations 

      Fröhlich, Christopher; Gama, João Alves; Harms, Klaus; Hirvonen, Viivi H. A.; Lund, Bjarte Aarmo; van der Kamp, Marc W.; Johnsen, Pål Jarle; Samuelsen, Ørjan; Leiros, Hanna-Kirsti S. (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-04-28)
      Our current understanding of how low antibiotic concentrations shape the evolution of contemporary β-lactamases is limited. Using the widespread carbapenemase OXA-48, we tested the long-standing hypothesis that selective compartments with low antibiotic concentrations cause standing genetic diversity that could act as a gateway to developing clinical resistance. Here, we subjected <i>Escherichia ...
    • Emergence and dissemination of antimicrobial resistance in Escherichia coli causing bloodstream infections in Norway in 2002–17: a nationwide, longitudinal, microbial population genomic study 

      Gladstone, Rebecca Ashley; McNally, Alan; Pöntinen, Anna Kaarina; Tonkin-Hill, Gerry; Lees, John A.; Skytén, Kusti Onni; Cléon, Francois Pierre Alexandre; Christensen, Martin Owczarek Korsner; Haldorsen, Bjørg; Bye, Kristina K.; Gammelsrud, Karianne Wiger; Hjetland, Reidar; Kümmel, Angela; Larsen, Hege; Lindemann, Paul Christoffer; Löhr, Iren Høyland; Marvik, Åshild; Nilsen, Einar; Noer, Marie Therese; Simonsen, Gunnar Skov; Steinbakk, Martin; Tofteland, Ståle; Vattøy, Marit; Bentley, Stephen D.; Croucher, Nicholas J.; Parkhill, Julian; Johnsen, Pål Jarle; Samuelsen, Ørjan; Corander, Jukka (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-05-10)
      Background - The clonal diversity underpinning trends in multidrug resistant Escherichia coli causing bloodstream infections remains uncertain. We aimed to determine the contribution of individual clones to resistance over time, using large-scale genomics-based molecular epidemiology.<p> <p>Methods - This was a longitudinal, E coli population, genomic, cohort study that sampled isolates from ...
    • Evolution of β-lactamase-mediated cefiderocol resistance 

      Frøhlich, Christopher; Sørum, Vidar; Tokuriki, Nobuhiko; Johnsen, Pål Jarle; Samuelsen, Ørjan (Journal article; Tidsskriftartikkel; Peer reviewed, 2022-07-11)
      Background: Cefiderocol is a novel siderophore β-lactam with improved hydrolytic stability toward β-lactamases, including carbapenemases, achieved by combining structural moieties of two clinically efficient cephalosporins, ceftazidime and cefepime. Consequently, cefiderocol represents a treatment alternative for infections caused by MDR Gram-negatives.<p> <p>Objectives: To study the role of ...
    • Evolutionary and functional history of the Escherichia coli K1 capsule 

      Alonso, Sergio Arredondo; Blundell-Hunter, George; Fu, Zuyi; Gladstone, Rebecca Ashley; Fillol-Salom, Alfred; Loraine, Jessica; Cloutman-Green, Elaine; Johnsen, Pål Jarle; Samuelsen, Ørjan; Pöntinen, Anna Kaarina; Cleon, Francois Pierre Alexandre; Chavez-Bueno, Susana; De la Cruz, Miguel A.; Ares, Miguel A.; Vongsouvath, Manivanh; Chmielarczyk, Agnieszka; Horner, Carolyne; Klein, Nigel; McNally, Alan; Reis, Joice N.; Penadés, José R.; Thomson, Nicholas R.; Corander, Jukka; Taylor, Peter W.; McCarthy, Alex J. (Journal article; Tidsskriftartikkel; Peer reviewed, 2023-06-15)
      Escherichia coli is a leading cause of invasive bacterial infections in humans. Capsule polysaccharide has an important role in bacterial pathogenesis, and the K1 capsule has been firmly established as one of the most potent capsule types in E. coli through its association with severe infections. However, little is known about its distribution, evolution and functions across the E. coli phylogeny, ...
    • Evolutionary Instability of Collateral Susceptibility Networks in Ciprofloxacin-Resistant Clinical Escherichia coli Strains 

      Sørum, Vidar; Øynes, Emma Lu; Sollied Møller, Anna; Harms, Klaus; Samuelsen, Ørjan; Podnecky, Nicole L.; Johnsen, Pål Jarle (Journal article; Tidsskriftartikkel; Peer reviewed, 2022-07-07)
      ABSTRACT Collateral sensitivity and resistance occur when resistance development toward one antimicrobial either potentiates or deteriorates the effect of others. Previous reports on collateral effects on susceptibility focus on newly acquired resistance determinants and propose that novel treatment guidelines informed by collateral networks may reduce the evolution, selection, and spread of ...
    • Fitness costs of various mobile genetic elements in Enterococcus faecium and Enterococcus faecalis 

      Starikova, Irina; Al-Haroni, Mohammed; Werner, Guido; Roberts, Adam P.; Nielsen, Kåre M.; Johnsen, Pål Jarle (Journal article; Tidsskriftartikkel; Peer reviewed, 2013-07-05)
      Objectives: To determine the fitness effects of various mobile genetic elements (MGEs) in Enterococcus faecium and Enterococcus faecalis when newly acquired. We also tested the hypothesis that the biological cost of vancomycin resistance plasmids could be mitigated during continuous growth in the laboratory.<p> <p>Methods: Different MGEs, including two conjugative transposons (CTns) of the Tn916 ...
    • Gene transfer potential of outer membrane vesicles of Acinetobacter baylyi and effects of stress on vesiculation 

      Fulsundar, Shweta; Harms, Klaus; Flaten, Gøril Eide; Johnsen, Pål Jarle; Chopade, Balu Ananda; Nielsen, Kaare Magne (Journal article; Tidsskriftartikkel; Peer reviewed, 2014)
    • A high-throughput multiplexing and selection strategy to complete bacterial genomes 

      Alonso, Sergio Arredondo; Pöntinen, Anna K.; Cleon, Francois Pierre Alexandre; Gladstone, Rebecca Ashley; Schürch, Anita C.; Johnsen, Pål Jarle; Samuelsen, Ørjan; Corander, Jukka (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-12-09)
      Background: Bacterial whole-genome sequencing based on short-read technologies often results in a draft assembly formed by contiguous sequences. The introduction of long-read sequencing technologies permits those contiguous sequences to be unambiguously bridged into complete genomes. However, the elevated costs associated with long-read sequencing frequently limit the number of bacterial isolates ...
    • Host dependent maintenance of a blaNDM-1-encoding plasmid in clinical Escherichia coli isolates 

      Alves Gama, Joao Pedro; Kloos, Julia Maria; Johnsen, Pål Jarle; Samuelsen, Ørjan (Journal article; Tidsskriftartikkel; Peer reviewed, 2020-06-09)
      Dissemination of bacterial clones carrying plasmid-mediated resistance genes is a major factor contributing to the increasing prevalence of antibiotic resistance. Understanding the evolution of successful clones and the association to mobile resistance elements are therefore crucial. In this study, we determined the sequence of a 145 kb IncC multi-drug resistance plasmid (pK71-77-1-NDM), harbouring ...
    • Mge-cluster: a reference-free approach for typing bacterial plasmids 

      Alonso, Sergio Arredondo; Gladstone, Rebecca Ashley; Pöntinen, Anna Kaarina; Gama, João Alves; Schürch, Anita C.; Lanza, Val F.; Johnsen, Pål Jarle; Samuelsen, Ørjan; Tonkin-Hill, Gerry; Corander, Jukka (Journal article; Tidsskriftartikkel; Peer reviewed, 2023-07-10)
      Extrachromosomal elements of bacterial cells such as plasmids are notorious for their importance in evolution and adaptation to changing ecology. However, high-resolution population-wide analysis of plasmids has only become accessible recently with the advent of scalable long-read sequencing technology. Current typing methods for the classification of plasmids remain limited in their scope which ...
    • Natural Transformation Facilitates Transfer of Transposons, Integrons and Gene Cassettes between Bacterial Species 

      Domingues, Sara; Harms, Klaus; Fricke, W. Florian; Johnsen, Pål Jarle; da Silva, Gabriela J.; Nielsen, Kåre M. (Journal article; Tidsskriftartikkel; Peer reviewed, 2012)
      We have investigated to what extent natural transformation acting on free DNA substrates can facilitate transfer of mobile elements including transposons, integrons and/or gene cassettes between bacterial species. Naturally transformable cells of Acinetobacter baylyi were exposed to DNA from integron-carrying strains of the genera Acinetobacter, Citrobacter, Enterobacter, Escherichia, Pseudomonas, ...
    • No effect of natural transformation on the evolution of resistance to bacteriophages in the Acinetobacter baylyi model system. 

      Mcleman, Amy; Sierocinski, Pawel; Hesse, E; Buckling, A; Perron, G; Hülter, Nils Fredrik; Johnsen, Pål Jarle; Vos, M (Journal article; Tidsskriftartikkel; Peer reviewed, 2016)
      The adaptive benefits of natural transformation, the active uptake of free DNA molecules from the environment followed by incorporation of this DNA into the genome, may be the improved response to selection resulting from increased genetic variation. Drawing analogies with sexual reproduction, transformation may be particularly beneficial when selection rapidly fluctuates during coevolution with ...
    • OXA-48-Mediated Ceftazidime-Avibactam Resistance Is Associated with Evolutionary Trade-Offs 

      Fröhlich, Christopher; Sørum, Vidar; Thomassen, Ane Molden; Johnsen, Pål Jarle; Samuelsen, Ørjan (Journal article; Tidsskriftartikkel; Peer reviewed, 2019-03-27)
      Infections due to carbapenemase-producing Gram-negative pathogens are associated with limited treatment options and consequently lead to increased mortality and morbidity. In response, combinations of existing β-lactams and novel β-lactamase inhibitors, such as ceftazidime-avibactam (CAZ-AVI), have been developed as alternative treatment options. To understand the development of resistance and ...
    • Persistence of a pKPN3-like CTX-M-15-encoding IncFIIK plasmid in a Klebsiella pneumonia ST17 host during two years of intestinal colonization 

      Löhr, Iren Høyland; Hülter, Nils Fredrik; Bernhoff, Eva; Johnsen, Pål Jarle; Sundsfjord, Arnfinn; Naseer, Mohammed Umaer (Journal article; Tidsskriftartikkel; Peer reviewed, 2015-03-04)
      Objectives To characterize the CTX-M-15-encoding plasmid in a Klebsiella pneumoniae ST17 strain, responsible for an outbreak at a Norwegian neonatal intensive care unit and subsequent colonization of affected children for up to two years. To identify plasmid-mediated features relevant for the outbreak dynamics, and to investigate the plasmids capability of horizontal transfer, its segregational ...
    • Piggybacking on Niche Adaptation Improves the Maintenance of Multidrug-Resistance Plasmids 

      Kloos, Julia Maria; Gama, João Alves; Hegstad, Joachim; Samuelsen, Ørjan; Johnsen, Pål Jarle (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-03-24)
      The persistence of plasmids in bacterial populations represents a puzzling evolutionary problem with serious clinical implications due to their role in the ongoing antibiotic resistance crisis. Recently, major advancements have been made toward resolving this “plasmid paradox” but mainly in a nonclinical context. Here, we propose an additional explanation for the maintenance of multidrug‐resistance ...