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.
Publications 2015- (group members in bold)
1. Pontinen AK., Gladstone RA., Pesonen H., Pesonen H., Cleon F., Kallonen T., Simonsen GS., Croucher N., McNally A., Johnsen PJ., Samuelsen Ø., and J. Corander. Modulation of multi- drug resistant clone success in Escherichia coli populations: a longitudinal multi-country genomic and antibiotic usage cohort study. Lancet Microbe Jan 4th 2024, https://doi.org/10.1016/ S2666-5247(23)00292-6.
2. Lorentzen ØM., Haukefer ASB., Johnsen PJ, and C. Fröhlich. The Biofilm Lifestyle Shapes the Evolution of b-lactamases. Genome Biology and Evolution, Volume 16, Issue 3, March 2024, evae030, https://doi.org/10.1093/gbe/evae030
3. Fröhlich C., Bunzel HA., Buda K., Mulholland AJ., van der Kamp MW., Johnsen PJ., Leiros HK., and N. Tokuriki. Epistasis Arises from Shifting the Rate-Limiting Step during Enzyme Evolution of a b-lactamase.Nature Catalysis, 2024, https://doi.org/10.1038/s41929-024-01117-4
4. Arredondo-Alonso S., Gladstone RA., Pontinen AK., Gama JA., Gladstone R., Harms K., Tonkin-Hill G, Thorpe H., Simonsen GS., Norwegian E. coli study group., Johnsen PJ., Samuelsen Ø., and J. Corander. Escherichia coli plasmidome maps the game of clones. bioRxiv, doi: https://doi.org/10.1101/2023.10.14.562336 Dec. 7th. 2023, in review
5. Liljegren M., Gama JA., Johnsen PJ, and K. Harms. The recombination initiation functions DprA and RecFOR suppress microindel mutations in Acinetobacter baylyi ADP1. bioRxiv, doi:https://doi.org/10.1101/2023.11.22.568220, Nov. 22, 2023, in review.
6. Winter MR., Vos M., Buckling A., Johnsen PJ, and K. Harms. Effect of Chemotherapeutic Agents on Natural Transformation Frequency in Acinetobacter baylyi. Access Microbiology (preprint, under review)https://doi.org/10.1099/acmi.0.000733.v1, Nov. 3, 2023.
7. Arredondo-Alonso S., Gladstone RA., Pontinen AK., Gama JA., Schurch AC., Lanza VF., Johnsen PJJ., Samuelsen Ø., Tonkin-Hill G., and J. Corander. Mge-cluster: a reference-free approach for typing bacterial plasmids. NAR Genomics and Bioinformatics. 2023.5 (3) 1. doi: https://doi.or g/10.1093/nar gab/lqad066
8. Arredondo-Alonso S., Blundell-Hunter G., Fu Z., Gladstone RA., Filol-Salom A., Loraine, J., Johnsen PJJ., Samuelsen Ø., Pontinen AK., Cleon F., Chavez-Bueno S., De la Cruz MA., Ares MA., Vongsouvath M., Cmielarczyk A., Horner C., Klein N., McNally A., Reis JN., Penades JR., Thomson N., Corander J., Taylor PW., and AJ McCarthy. Evolutionary and functional history of the Escherichia coli K1 capsule. Nature Communications, 2023. 14, 3294. doi: https://doi.org/10.1038/s41467-023-39052-w
9. Winter M., Harms K., Johnsen PJ, and M. Vos. Collection of Annotated Acinetobacter Genome Sequences. Microbiol Res Announcements. 2023. 12 (3), e01094-2. doi: https://doi.org/10.1128/mra.01094-22
10. Sørum V., Øynes EL., Møller AS., Harms K., Samuelsen Ø., Podnecky NL., and PJ Johnsen. Evolutionary Instability of Collateral Susceptibility Networks in Ciprofloxacin-Resistant Clinical Escherichia coli Strains. mBio. 2022. 13 (4), e00441-22. doi: https://doi.org/10.1128/mbio.00441-22
11. Fröhlich C., Sørum V., Tokuriki N., Johnsen PJ, and Ø. Samuelsen. Evolution of b-lactamase-mediated cefiderocol resistance. J Antimicrob Chemother. 77(9) 2429-2436, 2022. doi: https://doi.org/10.1093/jac/dkac221
12. Mäklin T., Thorpe HA., Pöntinen AK., Gladstone RA., Shao Y., Pesonen M., McNally A., Johnsen PJ., Samuelsen Ø., Lawley TD., Honkela A., and J Corander. Strong pathogen competition in neonatal gut colonization. Nature Communications. 2022. 13 (1), 7417. doi: https://doi.org/10.1038/s41467-022-35178-5
13. Winter M., Buckling A., Harms K., Johnsen PJ., and M Vos. Antimicrobial resistance acquisition via natural transformation: context is everything. Curr. Op. Microbiol. 2022. 64, 133-138. doi: https://doi.org/10.1016/j.mib.2021.09.009
14. Dey, H, D Simonovic, ISFNS Hagen, T Vasskog, EGA Fredheim, HM Blencke, T Anderssen, MB Strøm, T Haug. Synthesis and antimicrobial activity of short analogues of the marine antimicrobial peptide Turgencin A: Effects of SAR optimizations, Cys-Cys cyclization and lipopeptide modifications. Interntional Journal of Molecular Sciences, 2022, 23(22). doi: https://doi.org/10.3390/ijms232213844
15. Gudmundsdóttir JS., Fredheim EGA., Koumans CIM., Hegstad J., Tang PC., Andersson DI., Samuelsen Ø.,and PJ Johnsen. The chemotherapeutic drug methotrexate selects for antibiotic resistance. EBioMedicine(2021), 74:103742. doi: https://doi.org/10.1016/j.ebiom.2021.103742
16. Arredondo-Alonso S., Pöntinen AK., Cleon F., Gladstone RA., Schürch AC., Johnsen PJ., Samuelsen Ø.,and J. Corander. A high-throughput multi-plexing strategy to complete bacterial genomes. GigaScience, 10, 2021, 1–13. doi: https://doi.org/10.1093/gigascience/giab079
17. Kloos J., Gama JA., Hegstad J., Samuelsen, Ø., and PJ Johnsen. Piggybacking on niche- adaptation reduces the cost of multidrug resistance plasmids. Mol. Biol. Evol, 2021, 38, 8, 3188–3201. doi: https://doi.org/10.1093/molbev/msab091
18. Gladstone R., McNally A., Pöntinen AK., Tonkin-Hill G., Lees JA., Skytén KO., Cléon F., Christensen MOK., Haldorsen BC., Bye KK., Gammelsrud KW., Hjetland R., Kümmel A., Larsen HE., Lindemann PC., Löhr IH., Marvik Å., Nilsen E., Noer MT., Simonsen GS., Steinbakk M., Tofteland S., Vattøy M., Bentley SD., Croucher NJ., Parkhill J., Johnsen PJ., Samuelsen Ø., Corander J. Emergence and dissemination of antimicrobial resistance in Escherichia coli bloodstream infections: a nationwide longitudinal microbial population study in Norway between 2002-2017. Lancet Microbe (2021), 2(10), e492. doi: https://doi.org/10.1016/S2666-5247(21)00031-8
19. Fröhlich C., Gama J., Harms K., Hirvonen VHA., Lund BA., van der Kamp MW., Johnsen PJ., Samuelsen Ø, and HK Leiros. Cryptic β-Lactamase Evolution Is Driven by Low β- Lactam Concentrations. 2021. mSphere, 6 (2), 10.1128/msphere. 00108-21. doi: https://doi.org/10.1128/msphere.00108-21
20. PJ Johnsen, Gama J, and K. Harms. Bacterial evolution on demand. 2021. eLife, 10,e68070, invited commentary. doi: https://doi.org/10.7554/eLife.68070
21. Kloos J., Johnsen PJ., and K. Harms. Tn1 transposition in the course of natural transformationenables horizontal antibiotic resistance spread in Acinetobacter baylyi. 2021. Microbiology, 167 (1). doi: 10.1099/mic.0.001003
22. Gama J., Kloos J., Johnsen PJ., and Ø. Samuelsen. Host dependent maintenance of blaNDM- 1-encoding plasmid in clinical Escherichia coli isolates. 2020. Scientific Reports, 10 (1), 9332.https://doi.org/10.1038/s41598-020-66239-8
23. Obuobi, SAO, K Julin, EGA Fredheim, M Johannessen, N Skalko-Basnet. Liposomal delivery of antibiotic loaded nucleic acid nanogels with enhanced drug loading and synergistic anti-inflammatory activity against S. aureus intracellular infections. Journal of Controlled Release, 2020, 324:620-632. doi: https://doi.org/10.1016/j.jconrel.2020.06.002
24. Wolden R, M Pain, R Karlsson, A Karlson, EGA Fredheim, JP Cavanagh. Identification of surface proteins in a clinical Staphylococcus haemolyticus isolate by bacterial surface shaving. BMC Microbiology, 2020, 20(80); 1-18. doi: https://doi.org/10.1186/s12866-020-01778-8
25. Gama JA, EGA Fredheim, FPA Clèon, AM Reis, R Zilhão, F. Dionisio. Dominance between plasmids determines the extent of biofilm formation. Frontiers in Microbiology, 2020. doi: https://doi.org/10.3389/fmicb.2020.02070
26. Fröhlich C., AM.Thomassen., PJ Johnsen, HKLeiros and Ø.Samuelsen.OXA-48-mediated ceftazidime-avibactam resistance is associated with evolutionary trade-offs. 2019. mSphere, 4: e00024-19. doi: https://doi.org/10.1128/msphere.00024-19
27. Granslo, HN, EGA Fredheim, E Esaiassen, L Christophersen, PØ Jensen, TE Mollnes, C Moser, T Flægstad, C Klingenberg, JP Cavanagh. The synthetic antimicrobial peptide LTX21 induces inflammatory responses in a human whole blood model and murine peritoneum model. APMIS -Journal of Pathology, Microbiology and Immunology, 2019, 127(6);475-483. Doi: https://doi.org/10.1111/apm.12946
28. Podnecky NL, Fredheim EGA, Kloos J, Sørum V, Primicerio R, Roberts AP, Rozen DE, Samuelsen Ø, PJ Johnsen. Conserved collateral susceptibility networks in diverse clinical strains of Escherichia coli. Nature Communications, 2018. 9 (1), 3673. doi: https://doi.org/10.1038/s41467-018-06143-y
29. Hülter N., Sørum V., Borch-Pedersen K., Liljegren M., Utnes A.L.G., Primicerio R., Harms K., P. J. Johnsen. Costs and benefits of natural transformation in Acinetobacter baylyi. 2017. BMC Microbiology 17 (1), 34. doi: https://doi.org/10.1186/s12866-017-0953-2
30. Di Luca MC., Sørum V., Starikova I., Kloos J., Hülter N., Naseer U., Johnsen PJ., Ø. Samuelsen. Low biological cost of carbapenemase-encoding plasmids following transfer from Klebsiella pneumoniae to Escherichia coli. 2017. J Antimicrob Chemother, 2017 72:1 85-89. doi: https://doi.org/10.1093/jac/dkw350
31. Ambur O.H., Engelstädter J., Johnsen P. J., Miller E- L., Rozen D. E. Steady at the wheel: conservative sex and the benefits of bacterial transformation. 2016. Phil. Trans. R. Soc. B 371 (1706), 20150528. doi: https://doi.org/10.1098/rstb.2015.0528
32. Harms K., Lunnan A., Hülter N., Mourier T., Vinner L., Andam CP., Martiinen P., Fridholm H., Hansen AJ., Hanage WP., Nielsen KM., Willerslev E., PJ Johnsen. Substitutions of short Heterologous DNA segements of intragenomic or extragenomic origins produce clustered genomic polymorphisms. Proc Nat Acad Sci U S A, 2016 113:52 15066-07. doi: https://doi.org/10.1073/pnas.1615819114
33. Engelstädter J., Harms K., and PJ Johnsen. The evolutionary dynamics of integrons in changing environments ISME J, 2016 Feb 5. doi: 10.1038/ismej.2015.222.
34. Utnes A., Sorum V., Hulter N., Primicerio R., Kloos J., Nielsen K.M., and PJ Johnsen. Growth phase specific evolutionary benefits of natural transformation in Acinetobacter baylyi. ISME J, 2015; advance online publication 7 April 2015; doi: 10.1038/ismej.2015.35
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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
- 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
- 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.
- 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
- Engelstädter J., Harms K., Johnsen PJ. The evolutionary dynamics of integrons in changing environments ISME J, 2016, Jun;10(6):1296-307.
- 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.
- 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
- 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.
- 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.
- 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
- 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.
- 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
- 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
- Johnsen PJ., and Levin B. R. 2010. Adjusting to alien genes. Mol Microbiol. 75: 1061-63 Invited commentary
- 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.
- 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.
- 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
