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Bilde av Johnsen, Pål Jarle
Bilde av Johnsen, Pål Jarle
Professor Department of Pharmacy paal.johnsen@uit.no +4777623156 +47 47688974 You can find me here

Pål Jarle Johnsen

Job description

We do basic research on microbial evolution . We focus on two thematically overlapping areas:

Evolution, selection, and spread of antibiotic resistance

It is clear that the frequency of antimicrobial drug resistance in the community is associated with the total level of antimicrobial consumption. Not so clear is the association between reduced consumption levels and subsequent reduction in the frequency of resistance. We focus on different processes that may counteract the reversal of antimicrobial resistance in environments with reduced selective pressures such as the biological cost of resistance, horizontal gene transfer, and genetic stability of resistance determinants. Within this context we are currently working on transmission dynamics and molecular epidemiology of antimicrobial resistance genes/elements in bacterial populations as well as “collateral sensitivity” as a selection inversion strategy to reduce evolution, selection and spread of antibiotic resistance. Our recent work proves that antimicrobial resistance is not the only success factor of human pathogenic clones, hence we also study the role of other pathogenicity factors in selecting for and shaping the population of pathogenic clones such as bacteriocin production,  biofilm formation and immune interactions.

Mechanistic and evolutionary consequences of bacterial genome plasticity

Horizontal gene transfer (HGT) in bacteria plays a major role in adaptive evolution exemplified by the evolution, spread and selection for antibiotic resistance determinants. We focus on evolutionary dynamics of mobile genetic elements to understand the underlying evolutionary forces responsible for their maintenance in bacterial populations. We are also interested in the mechanistic basis of acquisition of foreign DNA in bacteria and how it affects genetic diversity in microbes.

 

  • Anna Kaarina Pöntinen, Rebecca Ashley Gladstone, Henri Pesonen, Maiju Pesonen, Francois Pierre Alexandre Cleon, Benjamin J Parcell et al.:
    Modulation of multidrug-resistant clone success in Escherichia coli populations: a longitudinal, multi-country, genomic and antibiotic usage cohort study
    Lancet Microbe 2024 ARKIV / DOI
  • Christopher Frøhlich, H. Adrian Bunzel, Karol Buda, Adrian J. Mulholland, Marc W. van der Kamp, Pål Jarle Johnsen et al.:
    Epistasis arises from shifting the rate-limiting step during enzyme evolution of a β-lactamase
    Nature Catalysis 2024 ARKIV / DOI
  • Øyvind Myrvoll Lorentzen, Anne Sofie B. Haukefer, Pål Jarle Johnsen, Christopher Frøhlich :
    The Biofilm Lifestyle Shapes the Evolution of β-Lactamases
    Genome Biology and Evolution (GBE) 2024 ARKIV / DOI
  • Mikkel Meyn Liljegren, João Alves Gama, Pål Jarle Johnsen, Klaus Harms :
    The recombination initiation functions DprA and RecFOR suppress microindel mutations in Acinetobacter baylyi ADP1
    Molecular Microbiology 2024 ARKIV / DOI
  • Mikkel Meyn Liljegren, João Alves Gama, Pål Jarle Johnsen, Klaus Harms :
    Plasmids affect microindel mutations in Acinetobacter baylyi ADP1
    Plasmid 2024 ARKIV / DOI
  • Sergio Arredondo Alonso, George Blundell-Hunter, Zuyi Fu, Rebecca Ashley Gladstone, Alfred Fillol-Salom, Jessica Loraine et al.:
    Evolutionary and functional history of the Escherichia coli K1 capsule
    Nature Communications 2023 ARKIV / DOI
  • Macaulay Winter, Klaus Harms, Pål Jarle Johnsen, Michiel Vos :
    Collection of Annotated Acinetobacter Genome Sequences
    Microbiology Resource Announcements (MRA) 2023 DOI
  • Sergio Arredondo Alonso, Rebecca Ashley Gladstone, Anna Kaarina Pöntinen, João Alves Gama, Anita C. Schürch, Val F. Lanza et al.:
    Mge-cluster: a reference-free approach for typing bacterial plasmids
    NAR Genomics and Bioinformatics 2023 ARKIV / DOI
  • Macaulay Winter, Klaus Harms, Pål Jarle Johnsen, Angus Buckling, Michiel Vos :
    Testing for the fitness benefits of natural transformation during community-embedded evolution
    Microbiology (Reading) 2023 ARKIV / DOI
  • Vidar Sørum, Emma Lu Øynes, Anna Sollied Møller, Klaus Harms, Ørjan Samuelsen, Nicole L. Podnecky et al.:
    Evolutionary Instability of Collateral Susceptibility Networks in Ciprofloxacin-Resistant Clinical Escherichia coli Strains
    mBio 2022 ARKIV / DOI
  • Tommi Mäklin, Harry Arthur Frank Wright Thorpe, Anna Kaarina Pöntinen, Rebecca Ashley Gladstone, Yan Shao, Maiju Pesonen et al.:
    Strong pathogen competition in neonatal gut colonisation
    Nature Communications 2022 ARKIV / DOI
  • Rebecca Ashley Gladstone, Alan McNally, Anna Kaarina Pöntinen, Gerry Tonkin-Hill, John A. Lees, Kusti Onni Skytén et al.:
    Emergence and dissemination of antimicrobial resistance in Escherichia coli causing bloodstream infections in Norway in 2002–17: a nationwide, longitudinal, microbial population genomic study
    Lancet Microbe 29. June 2021 FULLTEKST / ARKIV / DOI
  • Pål Jarle Johnsen, João Alves Gama, Klaus Harms :
    Bacterial evolution on demand
    eLIFE 2021 ARKIV / DOI
  • Macaulay Winter, Angus Buckling, Klaus Harms, Pål Jarle Johnsen, Michiel Vos :
    Antimicrobial resistance acquisition via natural transformation: context is everything
    Current Opinion in Microbiology 2021 ARKIV / DOI
  • Sergio Arredondo Alonso, Anna Kaarina Pöntinen, Francois Pierre Alexandre Cleon, Rebecca Ashley Gladstone, Anita C. Schürch, Pål Jarle Johnsen et al.:
    A high-throughput multiplexing and selection strategy to complete bacterial genomes
    GigaScience 2021 ARKIV / DOI
  • Jonina Gudmundsdottir, Elizabeth G. Aarag Fredheim, Catharina I.M. Koumans, Joachim Hegstad, Po-Cheng Tang, Dan I. Andersson et al.:
    The chemotherapeutic drug methotrexate selects for antibiotic resistance
    EBioMedicine 2021 ARKIV / DOI
  • Christopher Frøhlich, João Alves Gama, Klaus Harms, Viivi H. A. Hirvonen, Bjarte Aarmo Lund, Marc W. van der Kamp et al.:
    Cryptic β-Lactamase Evolution Is Driven by Low β-Lactam Concentrations
    mSphere 2021 ARKIV / DOI
  • Julia Kloos, João A Gama, Joachim Hegstad, Ørjan Samuelsen, Pål J Johnsen :
    Piggybacking on Niche Adaptation Improves the Maintenance of Multidrug-Resistance Plasmids
    Molecular Biology and Evolution (MBE) 2021 ARKIV / DOI
  • Julia Maria Kloos, Pål Jarle Johnsen, Klaus Harms :
    Tn1 transposition in the course of natural transformation enables horizontal antibiotic resistance spread in Acinetobacter baylyi
    Microbiology (Reading) 2020 ARKIV / DOI
  • Julia Maria Kloos, Joao Pedro Alves Gama, Pål Jarle Johnsen, Ørjan Samuelsen :
    Host dependent maintenance of a blaNDM-1-encoding plasmid in clinical Escherichia coli isolates
    Scientific Reports 2020 DOI
  • Joao Pedro Alves Gama, Julia Maria Kloos, Pål Jarle Johnsen, Ørjan Samuelsen :
    Host dependent maintenance of a blaNDM-1-encoding plasmid in clinical Escherichia coli isolates
    Scientific Reports 2020 ARKIV / DOI
  • Christopher Frøhlich, Vidar Sørum, Ane Molden Thomassen, Pål Jarle Johnsen, Hanna-Kirsti S. Leiros, Ørjan Samuelsen :
    OXA-48-Mediated Ceftazidime-Avibactam Resistance Is Associated with Evolutionary Trade-Offs
    mSphere 2019 ARKIV / DOI
  • Nicole L. Podnecky, Elizabeth Aarag, Julia Maria Kloos, Vidar Sørum, Raul Primicerio, Adam Paul Roberts et al.:
    Conserved collateral antibiotic susceptibility networks in diverse clinical strains of Escherichia coli.
    Nature Communications 10. September 2018 ARKIV / DOI
  • Nils Fredrik Hülter, Vidar Sørum, Kristina Borch-Pedersen, Mikkel Meyn Liljegren, Ane Utnes, Raul Primicerio et al.:
    Costs and benefits of natural transformation in Acinetobacter baylyi
    BMC Microbiology 2017 ARKIV / DOI
  • Christopher Frøhlich, H. Adrian Bunzel, Karol Buda, Adrian J. Mulholland, Marc W. van der Kamp, Pål Jarle Johnsen et al.:
    Correction to: Epistasis arises from shifting the rate-limiting step during enzyme evolution of a β-lactamase (Nature Catalysis, (2024), 10.1038/s41929-024-01117-4)
    Nature Catalysis 2024 DOI
  • Øyvind Myrvoll Lorentzen, Christopher Fröhlich, Anne Sofie Haukefer, Sören Abel, Pål Jarle Johnsen :
    Evolution of Vibrio cholerae biofilms
    2023
  • Øyvind Myrvoll Lorentzen, João Alves Gama, Klaus Harms, Sören Abel, Pål Jarle Johnsen :
    Genetic conflict between the SXT-element and a multidrug resistance plasmid in Vibrio cholerae
    2023
  • Øyvind Myrvoll Lorentzen, João Alves Gama, Klaus Harms, Sören Abel, Pål Jarle Johnsen :
    Genetic conflict between the SXT-element and a multidrug resistance plasmid in Vibrio cholerae
    2023
  • Christopher Frøhlich, Adrian Bunzel, Karol Buda, Pål Jarle Johnsen, Nobuhiko Tokuriki :
    Divergent genetic evolution employs the same molecular mechanisms
    2023
  • Julia Maria Kloos, Lea Jänisch, Anna Kaarina Pöntinen, Ørjan Samuelsen, Pål Jarle Johnsen, Jukka Corander et al.:
    Different metabolic proficiency among dominant ExPEC lineages
    2022
  • Christopher Frøhlich, Adrian H. Bunzel, Marc W. Van Der Kamp, Adrian J. Mulholland, Hanna-Kirsti Schrøder Leiros, Pål Jarle Johnsen et al.:
    Positive epistasis drives the molecular evolution of the carbapenemase OXA-48
    2022
  • Øyvind Myrvoll Lorentzen, Sören Abel, Pål Jarle Johnsen :
    Evolution of Vibrio cholerae biofilms
    2022
  • Klara Stensvåg, Arnfinn Sundsfjord, Pål Jarle Johnsen, Hanna-Kirsti S. Leiros, Lise Nordgård :
    CANS - Centre for New Antibacterial Strategies
    2022 PROSJEKT
  • Pål Jarle Johnsen, Elizabeth G Aarag Fredheim, Ørjan Samuelsen, Klaus Harms :
    The role of drugs used in cancer chemotherapy as drivers of antibiotic resistance evolution in Escherichia coli
    2022
  • João Alves Gama, Julia Maria Kloos, Joachim Hegstad, Ørjan Samuelsen, Pål Jarle Johnsen :
    Plasmid cost alleviation as a consequence of niche-adaptation
    2021
  • Julia Maria Kloos, João Alves Gama, Joachim Hegstad, Ørjan Samuelsen, Pål Jarle Johnsen :
    Plasmid Cost Alleviation By Hitchhiking On Niche-adaptation
    2021
  • Julia Maria Kloos, Joao Pedro Alves Gama, Joachim Hegstad, Ørjan Samuelsen, Pål Jarle Johnsen :
    E. coli Niche Adaptation Improves Plasmid Maintenance
    2021
  • Rebecca Ashley Gladstone, Alan McNally, Pål Jarle Johnsen, Ørjan Samuelsen, Jukka Corander :
    Antimicrobial resistance genes and clonal success in Escherichia coli isolates causing bloodstream infection – Authors’ reply
    Lancet Microbe 2021 DOI
  • Sybil Akua Okyerewa Obuobi, Kjersti Julin, Elizabeth G. Aarag Fredheim, Pål Jarle Johnsen, Mona Johannessen, Natasa Skalko-Basnet :
    Liposomal delivery of antibiotic loaded DNA nanogels against intracellular infections
    2020
  • Christopher Frøhlich, Hanna-Kirsti S. Leiros, Pål Jarle Johnsen, Ørjan Samuelsen :
    Sub-inhibitory concentrations of ceftazidime drive evolution of the OXA-48 carbapenemase
    2019
  • Vidar Sørum, Emma Lu Øynes, Anna Møller, Nicole L. Podnecky, Sören Abel, Ørjan Samuelsen et al.:
    Evolutionary stability of collateral susceptibility networks in clinical Escherichia coli strains
    2019
  • Elizabeth G. Aarag Fredheim, Nicole Podnecky, Angie Carola Alarcon Rios, Jessica Nguyen Tran, Chantal Verstappen, Klaus Harms et al.:
    Gentamicin collateral sensitivity of ciprofloxacin resistant Escherichia coli is opposed by the rapid development of gentamicin resistance
    2019
  • Vidar Sørum, Anna Sollied Møller, Sören Abel, Ørjan Samuelsen, Nicole L. Podnecky, Pål Jarle Johnsen :
    Evolutionary stability of collateral effects in ciprofloxacin resistant clinical Escherichia coli strains
    2019
  • Vidar Sørum, Anna Sollied Møller, Pål Jarle Johnsen, Ørjan Samuelsen, Sören Abel, Nicole L. Podnecky :
    Evolutionary stability of collateral effects in ciprofloxacin resistant clinical Escherichia coli strains
    2019
  • Christopher Frøhlich, Pål Jarle Johnsen, Hanna-Kirsti Schrøder Leiros, Ørjan Samuelsen :
    Evolution of OXA-48 under sub-MIC conditions
    2019
  • Christopher Frøhlich, Vidar Sørum, Hanna-Kirsti S. Leiros, Pål Jarle Johnsen, Ørjan Samuelsen :
    Development of OXA-48 mediated ceftazidme-avibactam resistance is associated with an evolutionary trade-off
    2018
  • Julia Maria Kloos, Joao Pedro Alves Gama, Ørjan Samuelsen, Pål Jarle Johnsen :
    Klebsiella pneumoniae MDR-encoding plasmids in clinical isolates of uropathogenic Escherichia coli: plasmid-host co-evolution and its effect on fitness cost of plasmid-mediated resistance
    2018
  • Julia Maria Kloos, Joao Pedro Alves Gama, Ørjan Samuelsen, Pål Jarle Johnsen :
    Plasmid-host co-evolution of Klebsiella pneumoniae MDR-encoding plasmids in clinical isolates of uropathogenic Escherichia coli: effect on fitness cost of plasmid-mediated resistance
    2018
  • Julia Maria Kloos, Kaare Magne Nielsen, Pål Jarle Johnsen, Klaus Harms :
    Natural transformation of Acinetobacter baylyi by transposons
    2017
  • Julia Maria Kloos, Kaare Magne Nielsen, Pål Jarle Johnsen, Klaus Harms :
    Transposition during natural transformation facilitates spread of antibiotic resistance determinants in Acinetobacter baylyi
    2016

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    Research interests

    I'm head of the Microbial Pharmacology and Population Biology Research Group (MicroPop) and generally interested in bacterial microevolution and focusing on two main topics. 

     

    1. Evolution, selection, and spread of antibiotic resistance: It is clear that the frequency of antimicrobial drug resistance in the community is associated with the total level of antimicrobial consumption. Not so clear is the association between reduced consumption levels and subsequent reduction in the frequency of resistance. We focus on different processes that may counteract the reversal of antimicrobial resistance in drug free environments such as the biological cost of resistance, horizontal gene transfer, and genetic stability of resistance determinants. We are currently expanding our activities to include approaches for optimized antimicrobial treatment informed by principles of evolutionary, and population biology.

    2.    Mechanistic and evolutionary consequences of bacterial recombination:  Horizontal gene transfer (HGT) in bacteria plays a major role in adaptive evolution exemplified by the evolution, spread and selection for antibiotic resistance determinants.  For two out of three described mechanisms of HGT, conjugation and transduction, gene recruitment through recombination is likely a coincidental byproduct of plasmids’ and phages’ need for continuous transmission to new hosts. The third mechanism of HGT, natural transformation, is a complex mechanism for DNA uptake that requires the concerted action of many chromosomal genes. On first consideration it appears evident that this mechanism for HGT has evolved to “sample the available sequence space” in order to increase the adaptation rates of transformable strains. However, other hypotheses exist for both the evolution and the maintenance of natural transformation in bacteria. We are currently testing a number of these hypotheses both experimentally and theoretically. We are also interested in the mechanistic basis of bacterial recombination and it affects genetic diversity in microbes.

    CV AND CURRENT POSITION

    2000-2004. 
Ph.D. Student
Supervisors Prof. Arnfinn Sundsfjord, Dr. Med. Gunnar Skov Simonsen

    2004-2005
. Post Doctoral Fellowship. Department of Pharmacology. Prof. Kaare M. Nielsen Lab, Institute of Pharmacy, University of Tromsø, Norway.

    2006-2008: Personal postdoc grant The Norwegian Research Council (NFR), including:

    2007-2008 
Visiting Post Doc. Bruce Levin Lab. Emory University, Atlanta, USA

    2008- Associate Professor of Microbiology. Research group for Microbiology, pharmaco- and molecular epidemiology, Department of Pharmacy, University of Tromsø. Group leader: Prof. Kaare M. Nielsen.

    2014- Associate Professor, Group Leader Microbial Pharmacology and Population Biology Research Group 

     

    2015: Full Professor, Group Leader Microbial Pharmacology and Population Biology Research Group 

     

    SELECTED PUBLICATIONS

    1. Harms K., Lunnan A.,Hülter N., Mourier T., Vinner L., Andam C.P., Marttinen P., Fridholm H., Hansen A.J.,  Hanage W.P., Nielsen K.M., Willerslev E., Johnsen P.J. Substitutions of short heterologous DNA segments of intra- or extragenomic origins produce clustered genomic polymorphisms. Proc Natl Acad Sci U S A, In press
    2. Ambur OH., Engelstädter J., Johnsen PJ., Miller EL., Rozen DE. Steady at the wheel: conservative sex and the benefits of natural transformation. Philos Trans R Soc Lond B Biol Sci. 2016 Oct 19;371(1706). pii: 20150528.
    3. Di Luca MC., Sørum V., Starikova I., Klos J., Hülter N., Naseer U., Johnsen PJ., Samuelsen Ø. Low biological cost of carbapenemase producing plasmids following transfer from Klebsiella pneumonia to Escherichia coli. J Antimicrob Chemother. 2016 Sep 2. pii: dkw350
    4. Engelstädter J., Harms K., Johnsen PJ. The evolutionary dynamics of integrons in changing environments ISME J, 2016, Jun;10(6):1296-307.
    5. Utnes A., Sorum V., Hulter N., Primicerio R., Kloos J., Nielsen K.M., Johnsen PJ. Growth phase specific evolutionary benefits of natural transformation in Acinetobacter baylyi.  ISME J, 2015;Oct;9(10):2221-31.
    6. Levin B. R., Baquero F., Johnsen PJ. A Model-Guided Analysis and Perspective on the Evolution and Epidemiology of Antibiotic Resistance and its Future. Invited Current Opin Microbiol. 2014: Jun;19:83-9
    7. Overballe-Petersen S., Harms K*., Orlando L. A., Mayar J. V., Rasmussen S., Dahl T. W., Rosing M. T., Poole A. M., Sicheritz-Ponten T., Brunak S., Inselmann S., de Vries J., Wackernagel W., Pybus O. G., Nielsen R., Johnsen P. J., Nielsen K. M., and Willerslev E. Bacterial natural transformation by highly fragmented and damaged DNA. Proc Natl Acad Sci U S A. 2013: 110(49):19860-5. doi: 10.1073/pnas.1315278110. Epub 2013 Nov 18.
    8. Starikova I., Al-Haroni M., Werner G., Roberts A. P., Sørum V., Nielsen K.M., Johnsen PJ. Fitness costs of mobile genetic elements in Enterococcus faecium and Enterococcus faecalis.J Antimicrob Chemother. 2013 Dec;68(12):2755-65. Epub 2013 Jul 5.
    9. Harms K., Starikova I., Johnsen PJ. Costly class 1 integrons and the domesticatioon of the functional integrase. Mob Genet Elements. 2013 Mar 1;3(2):e24774
    10. StarikovaI., Harms K., Lunde T. M., Haugen P., Primicerio R., Samuelsen Ø., Nielsen K. M, Johnsen PJ. 2012. A trade-off between the fitness cost of functional integrases and long-term stability of integrons. PloS Pathog.8(11):e1003043.
    11. Domingues S., Harms K., Fricke F. W., Johnsen P. J., da Silva G., and K. M. Nielsen. 2012. Natural Transformation Facilitates Transfer of Transposons, Integrons and Gene Cassettes between Bacterial Species. PloS Pathog. 8 (8): e1002837
    12. Johnsen PJ., Townsend J. P., Bøhn T., Simonsen G. S., Sundsfjord A., and Nielsen K. M. 2011. Retrospective evidence for a biolog10ical cost of vancomycin resistance in Enterococcus faecium. J. Antimicrobial Agents and Chemother. 66(3):608-10
    13. Johnsen PJ., and Levin B. R.  2010. Adjusting to alien genes. Mol Microbiol. 75: 1061-63 Invited commentary
    14. Ray, J. L., Harms K., O. G. Wikmark, Starikova I., Johnsen PJ Nielsen KM. 2009. Sexual isolation in Acinetobacter baylyi is locus-specific and varies 10 000-fold over the genome. Genetics. 182: 1165-81.
    15. Johnsen PJ., Townsend J., Bohn T., Simonsen GS., Sundsfjord A., Nielsen KM. 2009. Factors affecting the reversal of antimicrobial resistance. Lancet Infect. Dis. 9: 357-364.
    16. Johnsen PJ., Dubnau D., Levin BR. Episodic Selection and the Maintenance of Competence and Transformation in Bacillus subtilis. 2009. Genetics. 181: 1521-1533. Chosen as Editorial highlight for April 2009
    Researcher profile in Cristin

    Member of research group

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