• Bacterial genomic epidemiology with mixed samples 

      Mäklin, Tommi; Kallonen, Teemu; Alanko, Jarno; Samuelsen, Ørjan; Hegstad, Kristin; Mäkinen, Veli; Corander, Jukka; Heinz, Eva; Honkela, Antti (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-11-15)
      Genomic epidemiology is a tool for tracing transmission of pathogens based on whole-genome sequencing. We introduce the mGEMS pipeline for genomic epidemiology with plate sweeps representing mixed samples of a target pathogen, opening the possibility to sequence all colonies on selective plates with a single DNA extraction and sequencing step. The pipeline includes the novel mGEMS read binner for ...
    • Carbapenem resistance determinants acquired through novel chromosomal integrations in extensively drug-resistant pseudomonas aeruginosa 

      Janice, Jessin; Agyepong, Nicholas; Owusu-Ofori, Alex; Govinden, Usha; Essack, Sabiha; Samuelsen, Ørjan; Sundsfjord, Arnfinn; Pedersen, Torunn (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-06-17)
      Two novel bla<sub>DIM-1</sub>- or bla<SUB>IMP-1</SUB>-containing genomic islands (GIs) were discovered by whole-genome sequence analyses in four extensively drug-resistant (XDR) <i>Pseudomonas aeruginosa</i> isolates from inpatients at a tertiary hospital in Ghana. The strains were of sequence type 234 (ST234) and formed a phylogenetic clade together with ST111, which is recognized as a global ...
    • 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 ...
    • Community carriage of ESBL-producing Escherichia coli and Klebsiella pneumoniae: a cross-sectional study of risk factors and comparative genomics of carriage and clinical isolates 

      Raffelsberger, Niclas Peter; Buczek, Dorota Julia; Svendsen, Kristian; Småbrekke, Lars; Pöntinen, Anna Kaarina; Löhr, Iren Høyland; Andreassen, Lotte Leonore Eivindsdatter; Simonsen, Gunnar Skov; Sundsfjord, Arnfinn Ståle; Gravningen, Kirsten; Samuelsen, Ørjan (Journal article; Tidsskriftartikkel; Peer reviewed, 2023-06-12)
      The global prevalence of infections caused by extended-spectrum βlactamase-producing Enterobacterales (ESBL-E) is increasing, and for Escherichia coli, observations indicate that this is partly driven by community-onset cases. The ESBL-E population structure in the community is scarcely described, and data on risk factors for carriage are conflicting. Here, we report the prevalence and population ...
    • 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 ...
    • 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 ...
    • Crystal Structures of Pseudomonas aeruginosa GIM-1: Active-Site Plasticity in Metallo-beta-Lactamases 

      Borra, Naga Pardha Saradhi; Samuelsen, Ørjan; Spencer, James; Walsh, Timothy R.; Lorentzen, marit sjo; Leiros, Hanna-Kirsti S. (Journal article; Tidsskriftartikkel; Peer reviewed, 2013)
      Metallo- -lactamases (MBLs) have rapidly disseminated worldwide among clinically important Gram-negative bacteria and have challenged the therapeutic use of -lactam antibiotics, particularly carbapenems. The blaGIM-1 gene, encoding one such enzyme, was first discovered in a Pseudomonas aeruginosa isolate from 2002 and has more recently been reported in Enterobacteriaceae. Here, we present crystal ...
    • 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.
    • Detection of Klebsiella pneumoniae human gut carriage: a comparison of culture, qPCR, and whole metagenomic sequencing methods 

      Lindstedt, Kenneth; Buczek, Dorota Julia; Pedersen, Torunn Annie; Hjerde, Erik; Raffelsberger, Niclas Peter; Suzuki, Yutaka; Brisse, Sylvain; Holt, Kathryn E.; Samuelsen, Ørjan; Sundsfjord, Arnfinn (Journal article; Tidsskriftartikkel; Peer reviewed, 2022-08-31)
      Klebsiella pneumoniae is an important opportunistic healthcare-associated pathogen and major contributor to the global spread of antimicrobial resistance. Gastrointestinal colonization with K. pneumoniae is a major predisposing risk factor for infection and forms an important hub for the dispersal of resistance. Current culture-based detection methods are time consuming, give limited intra-sample ...
    • 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 ...
    • Dissemination of a Carbapenem-Resistant Acinetobacter baumannii Strain Belonging to International Clone II/Sequence Type 2 and Harboring a Novel AbaR4-Like Resistance Island in Latvia 

      Saule, Mara; Samuelsen, Ørjan; Dumpis, Uga; Sundsfjord, Arnfinn; Karlsone, Aija; Balode, Arta; Miklasevics, Edvins; Karah, Nabil (Journal article; Tidsskriftartikkel; Peer reviewed, 2013)
      An outbreak of hospital-acquired Acinetobacter baumannii infections, caused by a blaOXA-23-positive carbapenem-resistant strain belonging to international clone II/ST2, was detected in Latvia. The strain was partially equipped with the armA gene and the intI1-aacA4-catB8-aadA1-qacE 1 class 1 integron. In addition, the strain carried AbaR25, a novel AbaR4-like resistance island of 46,500 bp ...
    • Efficacy of mecillinam against clinical multidrug-resistant Escherichia coli in a murine urinary tract infection model 

      Zykov, Ilya Nikolaevich; Frimodt-Møller, Niels; Småbrekke, Lars; Sundsfjord, Arnfinn; Samuelsen, Ørjan (Journal article; Tidsskriftartikkel; Peer reviewed, 2019-11-23)
      Pivmecillinam, a pro-drug of mecillinam, has been used extensively in Scandinavia for the treatment of acute lower urinary tract infections (UTIs) caused by Enterobacterales. It is still an attractive first-line drug for the empirical treatment of UTIs owing to the low prevalence of resistance as well as its favourable impact on the intestinal microbiota as a pro-drug and good in vitro efficacy ...
    • 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 ...
    • 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 ...