• 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 ...
    • Complete Genome Sequence of Pseudomonas aeruginosa K34-7, a Carbapenem-Resistant Isolate of the High-Risk Sequence Type 233 

      Taiaroa, George; Samuelsen, Ørjan; Kristensen, Tom; Økstad, Ole Andreas; Heikal, Adam (Journal article; Tidsskriftartikkel; Peer reviewed, 2018-08-02)
      Carbapenem-resistant Pseudomonas aeruginosa is defined as a “critical” priority pathogen for the development of new antibiotics. Here we report the complete genome sequence of an extensively drug-resistant, Verona integron-encoded metallo-β-lactamase-expressing isolate belonging to the high-risk sequence type 233.
    • 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, ...
    • The COVID-19 Pandemic Sparked off a Large-Scale Outbreak of Carbapenem-Resistant Acinetobacter baumannii from the Endemic Strains at an Italian Hospital 

      Petazzoni, Greta; Bellinzona, Greta; Merla, Cristina; Corbella, Marta; Monzillo, Vincenzina; Samuelsen, Ørjan; Corander, Jukka; Sassera, Davide; Gaiarsa, Stefano; Cambieri, Patrizia (Journal article; Tidsskriftartikkel; Peer reviewed, 2023-03-23)
      Acinetobacter baumannii is a nosocomial pathogen that poses a serious threat due to the rise of incidence of multidrug-resistant (MDR) strains. During the COVID-19 pandemic, MDR A. baumannii clones have caused several outbreaks worldwide. Here, we describe a detailed investigation of an MDR A. baumannii outbreak that occurred at Policlinico San Matteo (Pavia, Italy). A total of 96 A. baumannii ...
    • Cross-border spread of blaNDM-1- and blaOXA-48-positive Klebsiella pneumoniae: a European collaborative analysis of whole genome sequencing and epidemiological data, 2014 to 2019 

      Ludden, Catherine; Lötsch, Felix; Alm, Erik; Kumar, Narender; Johansson, Karin; Albiger, Barbara; Huang, Te-Din; Denis, Olivier; Hammerum, Anette M.; Hasman, Henrik; Jalava, Jari; Räisänen, Kati; Dortet, Laurent; Jousset, Agnès B.; Gatermann, Sören; Haller, Sebastian; Cormican, Martin; Brennan, Wendy; Grosso, Maria Del; Monaco, Monica; Schouls, Leo; Samuelsen, Ørjan; Pirš, Mateja; Cerar, Tjaša; Oteo-Iglesias, Jésus; Pérez-Vázquez, Maria; Sjöström, Karin; Edquist, Petra; Hopkins, Katie L.; Struelens, Marc J.; Palm, Daniel; Monnet, Dominique L.; Kohlenberg, Anke (Journal article; Tidsskriftartikkel; Peer reviewed, 2020-05-21)
      An alert regarding an outbreak of carbapenem-resistant <i>Klebsiella pneumoniae</i> carrying <i>bla</i> <sub>NDM-1</sub> and <i>bla</i> <sub>OXA-48</sub> carbapenemase-encoding genes was sent by Germany to European Union (EU)/European Economic Area (EEA) countries in October 2019. Since only limited whole genome sequencing (WGS) data on <i>bla</i> <sub>NDM-1-</sub> and <i>bla</i> <sub>OXA-48</sub>-positive ...
    • Detection of carbapenemases with a newly developed commercial assay using Matrix Assisted Laser Desorption Ionization-Time of Flight 

      Rapp, Ellionor; Samuelsen, Ørjan; Sundqvist, Martin (Journal article; Tidsskriftartikkel; Peer reviewed, 2018-02-03)
      This study evaluated the performance of the MBT STAR-Carba kit (Bruker Daltonics), to detect carbapenemase producing Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter spp. in comparison with the RAPIDEC® CARBA NP test (BioMerieux). MBT STAR-Carba allowed the detection of carbapenemases in Enterobacteriaceae and P. aeruginosa.
    • Dissemination and Characteristics of a Novel Plasmid-Encoded Carbapenem-Hydrolyzing Class D β-Lactamase, OXA-436, Found in Isolates from Four Patients Involving Six Different Hospitals in Denmark. 

      Samuelsen, Ørjan; Hansen, Frank; Aasnæs, Bettina; Hasman, Henrik; Lund, Bjarte Aarmo; Leiros, Hanna-Kirsti S.; Lilje, Berit; Janice, Jessin; Jakobsen, Lotte; Littauer, Pia; Søes, Lillian M; Holzknecht, Barbara J.; Andersen, Leif P; Stegger, Marc; Andersen, Paal S.; Hammerum, Anette M. (Journal article; Tidsskriftartikkel; Peer reviewed, 2017-10-23)
      The diversity of OXA-48-like carbapenemases are continually expanding. In this study, we describe the dissemination and characteristics of a novel class D carbapenemase (CHDL) named OXA-436. In total, six OXA-436-producing Enterobacteriaceae isolates including Enterobacter asburiae (n=3), Citrobacter freundii (n=2) and Klebsiella pneumoniae (n=1) were identified in four patients in the period between ...
    • 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 ...
    • Escherichia coli Sequence Type 410 Is Causing New International High-Risk Clones 

      Roer, Louise; Overballe-Petersen, Søren; Hansen, Frank; Schønning, Kristian; Wang, Mikala; Røder, Bent L; Hansen, , Dennis S; Justesen, Ulrik S; Andersen, Leif P; Fulgsang-Damgaard, David; Hopkins, Katie L; Woodford, Neil; Falgenhauer, Linda; Chakraborty, Trinad; Samuelsen, Ørjan; Sjöström, Karin; Johannesen, Thor B; Ng, Kim; Nielsen, Jens; Ethelberg, Steen; Stegger, Marc; Hammerum, Anette M.; Hasman, Henrik (Journal article; Tidsskriftartikkel; Peer reviewed, 2018-07-18)
      <i>Escherichia coli</i> sequence type 410 (ST410) has been reported worldwide as an extraintestinal pathogen associated with resistance to fluoroquinolones, third-generation cephalosporins, and carbapenems. In the present study, we investigated national epidemiology of ST410 <i>E. coli</i> isolates from Danish patients. Furthermore, <i>E. coli</i> ST410 was investigated in a global context to provide ...
    • 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 ...
    • 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 ...
    • Impact of extensive antibiotic treatment on faecal carriage of antibiotic-resistant enterobacteria in children in a low resistance prevalence setting 

      Knudsen, Per Kristian; Brandtzæg, Petter; Høiby, Ernst Arne; Bohlin, Jon; Samuelsen, Ørjan; Steinbakk, Martin; Abrahamsen, Tore G; Müller, Fredrik; Gammelsrud, Karianne Wiger (Journal article; Tidsskriftartikkel; Peer reviewed, 2017-11-07)
      We prospectively studied the consequences of extensive antibiotic treatment on faecal carriage of antibiotic-resistant enterobacteria in a cohort of children with cystic fibrosis (CF) and a cohort of children with cancer compared to healthy children with no or low antibiotic exposure. The study was conducted in Norway in a low resistance prevalence setting. Sixty longitudinally collected faecal ...
    • Metallo-β-lactamase inhibitors by bioisosteric replacement: preparation, activity and binding 

      Skagseth, Susann; Akhter, Sundus; Paulsen, Marianne H; Muhammad, Zeeshan; Samuelsen, Ørjan; Leiros, Hanna-Kirsti S.; Bayer, Annette (Journal article; Tidsskriftartikkel; Peer reviewed, 2017-04-14)
      Bacterial resistance is compromising the use of β-lactam antibiotics including carbapenems. The main resistance mechanism against β-lactams is hydrolysis of the β-lactam ring mediated by serine- or metallo-β-lactamases (MBLs). Although several inhibitors of MBLs have been reported, none has been developed into a clinically useful inhibitor. Mercaptocarboxylic acids are among the most prominent ...
    • 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 ...
    • Performance of the EUCAST disc diffusion method and two MIC methods in detection of Enterobacteriaceae with reduced susceptibility to meropenem: the NordicAST CPE study. 

      Haldorsen, Bjørg; Giske, Christian G; Hansen, Dennis S; Helgason, Kristjan Orri; Kahlmeter, Gunnar; Löhr, Iren Høyland; Matuschek, Erika; Österblad, Monica; Rantakokko-Jalava, Kaisu; Wang, Mikala; Småbrekke, Lars; Samuelsen, Ørjan; Sundsfjord, Arnfinn (Journal article; Tidsskriftartikkel; Peer reviewed, 2018-07-24)
      Objectives: To examine performance of EUCAST disc diffusion and supplementary MIC methods for detection of Enterobacteriaceae with reduced susceptibility to meropenem using EUCAST screening recommendations.<p> <p>Methods: Sixty-one Nordic laboratories delivered data on EUCAST disc diffusion (n " 61), semi-automated meropenem MIC (n " 23; VITEK2, n " 20 and Phoenix, n " 3) and gradient meropenem ...
    • Pharmacokinetics and pharmacodynamics of fosfomycin and its activity against extended-spectrum-lactamase-, plasmid-mediated AmpC-, and carbapenemase-producing escherichia coli in a murine urinary tract infection model 

      Zykov, Ilya Nikolaevich; Samuelsen, Ørjan; Jakobsen, Lotte; Småbrekke, Lars; Andersson, Dan I.; Sundsfjord, Arnfinn; Frimodt-Møller, Niels (Journal article; Tidsskriftartikkel; Peer reviewed, 2018-05-25)
      Fosfomycin has become an attractive treatment alternative for urinary tract infections (UTIs) due to increasing multidrug resistance (MDR) in <i>Escherichia coli</i>. In this study, we evaluated the pharmacokinetic (PK) and pharmacodynamic (PD) indices of fosfomycin and its <i>in vivo</i> activity in an experimental murine model of ascending UTI. Subcutaneous administration of fosfomycin showed that ...
    • Phenotypic and genotypic characterisation of thymine auxotrophy in Escherichia coli isolated from a patient with recurrent bloodstream infection 

      Jakovljev, Aleksandra; Afset, Jan Egil; Haugum, Kjersti; Steinum, Harald Otto; Rønning, Torunn Gresdal; Samuelsen, Ørjan; Ås, Christina Gabrielsen (Journal article; Tidsskriftartikkel; Peer reviewed, 2022-07-08)
      Introduction<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 ...
    • 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 ...