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Johnsen, Pål Jarle

Professor
Institutt for farmasi

Stillingsbeskrivelse:

Professor, Head of Microbial Pharmacology and Population Biology Research Group (MicroPop).




Forskningsinteresser

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 faeciumJ. 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

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  • Mcleman, Amy; Sierocinski, Pawel; Hesse, E; Buckling, A; Perron, G; Hülter, Nils Fredrik; Johnsen, Pål Jarle; Vos, M. No effect of natural transformation on the evolution of resistance to bacteriophages in the Acinetobacter baylyi model system.. Scientific Reports 2016; Volum 6. ISSN 2045-2322.s doi: 10.1038/srep37144.

  • Harms, Klaus; Lunnan, Asbjørn; Hulter, Nils; Mourier, Tobias; Vinner, Lasse; Andam, Cheryl P; Marttinen, Pekka; Fridholm, Helena; Hansen, Anders Johannes; Hanage, William P; Nielsen, Kaare Magne; Willerslev, Eske; Johnsen, Pål Jarle. Substitutions of short heterologous DNA segments of intragenomic or extragenomic origins produce clustered genomic polymorphisms. Proceedings of the National Academy of Sciences of the United States of America 2016; Volum 113 (52). ISSN 0027-8424.s 15066 - 15071.s doi: 10.1073/pnas.1615819114.

  • Ambur, Ole Herman; Engelstädter, Jan; Johnsen, Pål Jarle; Miller, Eric L.; Rozen, Daniel E.. Steady at the wheel: Conservative sex and the benefits of bacterial transformation. Philosophical Transactions of the Royal Society of London. Biological Sciences 2016; Volum 371:20150528 (1706). ISSN 0962-8436.s doi: 10.1098/rstb.2015.0528.

  • Engelstädter, Jan; Harms, Klaus; Johnsen, Pål Jarle. The evolutionary dynamics of integrons in changing environments. The ISME Journal 2016; Volum 10 (6). ISSN 1751-7362.s 1296 - 1307.s doi: 10.1038/ismej.2015.222.

  • Di Luca, Maria Chiara; Sørum, Vidar; Starikova, Irina; Kloos, Julia Maria; Hülter, Nils Fredrik; Naseer, Mohammed Umaer; Johnsen, Pål Jarle; Samuelsen, Ørjan. Low biological cost of carbapenemase-encoding plasmids following transfer from Klebsiella pneumoniae to Escherichia coli.. Journal of Antimicrobial Chemotherapy 2016; Volum 72. ISSN 0305-7453.s 85 - 89.s doi: 10.1093/jac/dkw350.

  • Borruso, Luigimaria; Harms, Klaus; Johnsen, Pål Jarle; Nielsen, Kaare Magne; Brusetti, Lorenzo. Distribution of class 1 integrons in a highly impacted catchment. (fulltekst) Science of the Total Environment 2016; Volum 566-567. ISSN 0048-9697.s 1588 - 1594.s doi: 10.1016/j.scitotenv.2016.06.054.

  • Löhr, Iren Høyland; Hülter, Nils Fredrik; Bernhoff, Eva; Johnsen, Pål Jarle; Sundsfjord, Arnfinn; Naseer, Mohammed Umaer. Persistence of a pKPN3-like CTX-M-15-encoding IncFIIK plasmid in a Klebsiella pneumonia ST17 host during two years of intestinal colonization. (fulltekst) PLoS ONE 2015; Volum 10 (3). ISSN 1932-6203.s doi: 10.1371/journal.pone.0116516.

  • Utnes, Ane Live Gunnes; Sørum, Vidar; Hülter, Nils Fredrik; Primicerio, Raul; Hegstad, Joachim; Kloos, Julia Maria; Nielsen, Kaare Magne; Johnsen, Pål Jarle. Growth phase-specific evolutionary benefits of natural transformation in Acinetobacter baylyi. The ISME Journal 2015; Volum 9 (10). ISSN 1751-7362.s 2221 - 2231.s doi: 10.1038/ismej.2015.35.

  • Levin, Bruce R:; Baquero, Fernando; Johnsen, Pål Jarle. A model-guided analysis and perspective on the evolution and epidemiology of antibiotic resistance and its future. Current Opinion in Microbiology 2014; Volum 19 (1). ISSN 1369-5274.s 83 - 89.s doi: 10.1016/j.mib.2014.06.004.

  • Fulsundar, Shweta; Harms, Klaus; Flaten, Gøril Eide; Johnsen, Pål Jarle; Chopade, Balu Ananda; Nielsen, Kaare Magne. Gene transfer potential of outer membrane vesicles of Acinetobacter baylyi and effects of stress on vesiculation. Applied and Environmental Microbiology 2014; Volum 80 (11). ISSN 0099-2240.s 3469 - 3483.s doi: 10.1128/AEM.04248-13.

  • Overballe-Petersen, Søren; Harms, Klaus; Orlando, Ludovic A.A.; Mayar, J. Victor Moreno; Rasmussen, Simon; Dahl, Tais W.; Rosing, Minik T.; Poole, Anthony M.; Sicheritz-Ponten, Thomas; Brunak, Søren; Inselmann, Sabrina; De Vries, Johann; Wackernagel, Wilfried; Pybus, Oliver G.; Nielsen, Rasmus; Johnsen, Pål Jarle; Nielsen, Kåre M.; Willerslev, Eske. Bacterial natural transformation by highly fragmented and damaged DNA. Proceedings of the National Academy of Sciences of the United States of America 2013; Volum 110 (49). ISSN 0027-8424.s 19860 - 19865.s doi: 10.1073/pnas.1315278110.

  • Starikova, Irina; Al-Haroni, Mohammed; Werner, Guido; Roberts, Adam P.; Sørum, Vidar; Nielsen, Kåre M.; Johnsen, Pål Jarle. Fitness costs of various mobile genetic elements in Enterococcus faecium and Enterococcus faecalis. Journal of Antimicrobial Chemotherapy 2013; Volum 68 (12). ISSN 0305-7453.s 2755 - 2765.s doi: 10.1093/jac/dkt270.

  • Hurler, Julia; Berg, Ole Alexander; Skar, Merete L.; Conradi, Anne Hilde; Johnsen, Pål Jarle; Skalko-Basnet, Natasa. Improved burns therapy: Liposomes-in-hydrogel delivery system for mupirocin. Journal of Pharmaceutical Sciences 2012; Volum 101 (10). ISSN 0022-3549.s 3906 - 3915.s doi: 10.1002/jps.23260.

  • Starikova, Irina; Harms, Klaus; Haugen, Pål; Lunde, Tracy Munthali; Primicerio, Raul; Samuelsen, Ørjan; Nielsen, Kaare Magne; Johnsen, Pål Jarle. A Trade-off between the Fitness Cost of Functional Integrases and Long-trem stability of Integrons. PLoS Pathogens 2012; Volum 8 (11). ISSN 1553-7366.s doi: 10.1371/journal.ppat.1003043.

  • Nielsen, Kåre M.; Ray, Jessica Louise; Johnsen, Pål Jarle. Horizontal gene transfer: the uptake of extracellular DNA in bacteria. Elsevier 2012 ISBN 9780123838780.

  • Domingues, Sara; Harms, Klaus; Fricke, W. Florian; Johnsen, Pål Jarle; da Silva, Gabriela J.; Nielsen, Kåre M.. Natural Transformation Facilitates Transfer of Transposons, Integrons and Gene Cassettes between Bacterial Species. PLoS Pathogens 2012; Volum 8 (8). ISSN 1553-7366.s doi: 10.1371/journal.ppat.1002837.

  • Johnsen, Pål jarle; Townsend, JP; Bøhn, Thomas; Simonsen, Gunnar Skov; Sundsfjord, arnfinn; Nielsen, Kaare Magne. Retrospective evidence for a biological cost of vancomycin resistance determinants in the absence of glycopeptide selective pressures. Journal of Antimicrobial Chemotherapy 2011; Volum 66 (3). ISSN 0305-7453.s 608 - 610.s doi: 10.1093/jac/dkq512.

  • Rosvoll, Torill Cathrin Solvær; Pedersen, Torunn; Sletvold, Hege; Johnsen, Pål Jarle; Sollid, Johanna U Ericson; Simonsen, Gunnar Skov; Jensen, Lars B; Nielsen, Kaare Magne; Sundsfjord, Arnfinn. PCR-based plasmid typing in Enterococcus faecium strains reveals widely distributed pRE25-, pRUM-, pIP501-and pHT beta-related replicons associated with glycopeptide resistance and stabilizing toxin-antitoxin systems. FEMS Immunology and Medical Microbiology 2010; Volum 58 (2). ISSN 0928-8244.s 254 - 268.s doi: 10.1111/j.1574-695X.2009.00633.x.

  • Sletvold, H; Johnsen, PJ; Wikmark, Odd-Gunnar; Simonsen, Gunnar Skov; Sundsfjord, A; Nielsen, KM. Tn1546 is part of a larger plasmid-encoded genetic unit horizontally disseminated among clonal Enterococcus faecium lineages. Journal of Antimicrobial Chemotherapy 2010; Volum 65 (9). ISSN 0305-7453.s 1894 - 1906.s doi: 10.1093/jac/dkq219.

  • Johnsen, Pål jarle; Townsend, Jeffrey P.; Bøhn, Thomas; Simonsen, Gunnar Skov; Sundsfjord, Arnfinn; Sundsfjord, arnfinn; Nielsen, Kaare Magne. Factors affecting the reversal of antimicrobial-drug resistance. Lancet. Infectious diseases (Print) 2009; Volum 9 (6). ISSN 1473-3099.s 357 - 364.

  • Nielsen, Kaare Magne; Ray, Jessica Louise; Johnsen, Pål jarle. Horizontal Gene Transfer: Uptake of Extracellular DNA by Bacteria. Elsevier 2009 ISBN 978-0-12-373944-5.s 587 - 596.

  • Johnsen, Pål jarle; Dubnau, Dave; Levin, Bruce R. Episodic Selection and the Maintenance of Competence and Natural Transformation in Bacillus subtilis. Genetics 2009; Volum 181 (4). ISSN 0016-6731.s 1521 - 1533.s doi: 10.1534/genetics.108.099523.

  • Ray, Jessica Louise; Harms, Klaus; Wikmark, Odd-Gunnar; Starikova, Irina; Johnsen, Pål jarle; Nielsen, Kaare Magne. Sexual Isolation in Acinetobacter baylyi Is Locus-Specific and Varies 10,000-Fold Over the Genome. Genetics 2009; Volum 182 (4). ISSN 0016-6731.s 1165 - 1181.s doi: 10.1534/genetics.109.103127.

  • Sletvold, H; Johnsen, PJ; Hamre, I; Simonsen, Gunnar Skov; Sundsfjord, Arnfinn; Nielsen, KM. Complete sequence of Enterococcus faecium pVEF3 and the detection of an omega-epsilon-zeta toxin-antitoxin module and an ABC transporter. Plasmid 2008; Volum 60 (1). ISSN 0147-619X.s 75 - 85.s doi: 10.1016/j.plasmid.2008.04.002.

  • Brusetti, Lorenzo; Glad, trine; Brodin, Sara; Myren, Petter; Rizzi, Aurora; Johnsen, Pål jarle; Carter, Phil; Daffonchio, Daniele; Nielsen, Kaare Magne. Low prevalence of blaTEM genes in Arctic environments and agricultural soil and rhizosphere. Microbial Ecology in Health and Disease 2008; Volum 20 (1). ISSN 0891-060X.s 27 - 36.s doi: 10.1080/08910600701838244.

  • Sletvold, H; Johnsen, PJ; Simonsen, Gunnar Skov; Aasnæs, B; Sundsfjord, Arnfinn; Nielsen, KM. Comparative DNA analysis of two vanA plasmids from Enterococcus faecium strains isolated from poultry and a poultry farmer in Norway. Antimicrobial Agents and Chemotherapy 2007; Volum 51 (2). ISSN 0066-4804.s 736 - 739.s doi: 10.1128/AAC.00557-06.

  • Nielsen, Kaare Magne; Johnsen, Pål jarle; Van Elsas, Jan Dirk. Horizontal gene transfer and microevolution in Soil. CRC Press 2007 ISBN 978-0-8247-2749-9.s 55 - 81.

  • Dahl, Kristin Hegstad; Mater, DDG; Flores, MJ; Johnsen, Pål jarle; Midtvedt, T; Corthier, G; Sundsfjord, arnfinn. Transfer of plasmid and chromosomal glycopeptide resistance determinants occurs more readily in the digestive tract of mice than in vitro and exconjugants can persist stably in vivo in the absence of glycopeptide selection. Journal of Antimicrobial Chemotherapy 2007; Volum 59. ISSN 0305-7453.s doi: 10.1093/jac/dkl530.

  • Nielsen, Kaare Magne; Johnsen, Pål jarle; Bensasson, Douda; Daffonchio, Daniele. Release and persistence of extracellular DNA in the environment. Environmental Biosafety Research 2007; Volum 6. ISSN 1635-7922.s 37 - 53.

  • Sørum, Marit; Johnsen, PJ; Aasnes, Bettina; Rosvoll, T; Kruse, H; Sundsfjord, Arnfinn; Simonsen, Gunnar Skov. Prevalence, persistence, and molecular characterization of glycopeptide-resistant enterococci in Norwegian poultry and poultry farmers 3 to 8 years after the ban on avoparcin. Applied and Environmental Microbiology 2006; Volum 72. ISSN 0099-2240.

  • Johnsen, Pål Jarle; Østerhus, Jan Ivar; Sletvold, Hege; Sørum, Marit; Kruse, Hilde; Nielsen, Kaare Magne; Simonsen, Gunnar Skov; Sundsfjord, Arnfinn. Persistence of animal and human glycopeptide-resistant enterococci on two Norwegian poultry farms formerly exposed to avoparcin is associated with a widespread plasmid-mediated vanA element within a polyclonal Enterococcus faecium population. Applied and Environmental Microbiology 2005; Volum 71 (1). ISSN 0099-2240.s 159 - 168.

  • Harms, Klaus; Starikova, Irina; Johnsen, Pål Jarle. Costly Class-1 integrons and the domestication of the the functional integrase. Mobile Genetic Elements 2013; Volum 3 (2). ISSN 2159-2543.s doi: 10.4161/mge.24774.

  • Johnsen, Pål Jarle. Is it more to bacterial sex than exploring the fitness landscape of other organisms?. 2012 ISBN 3923022360.s 1 - 13.

  • Johnsen, Pål jarle; Levin, Bruce R. Adjusting to alien genes. Molecular Microbiology 2010; Volum 75 (5). ISSN 0950-382X.s 1061 - 1063.s doi: 10.1111/j.1365-2958.2010.07075.x.

  • Johnsen, Pål jarle. The cost of antibiotic resistance; a bacterial perspective. Invited speaker at Eastman dental Institute Research Seminar series, University College of London. Seminar 2009-03-04 - 2009.

  • Sletvold, hege; Johnsen, Pål jarle; Simonsen, Gunnar Skov; Sundsfjord, arnfinn; Nielsen, Kaare Magne. Complete DNA sequence of the Enterococcus faecium vanA plasmid pIP816, and comparative analyses to vanA plasmids isolated from poultry farmer E. faecium strains. Plasmid 2007; Volum 57 (2). ISSN 0147-619X.s 239 - 239.

  • Sletvold, hege; Johnsen, Pål jarle; Simonsen, Gunnar Skov; AasnÆs, bettina; Sundsfjord, Arnfinn; Nielsen, Kaare Magne. Complete nucleotide sequence of the VanA glycopeptide resistance-mediating plasmid p399/F99/A9 from Enterococcus faecium. ASM-FEMS Conference on Enterococci 2005-08-28 - 2005-08-31 2005.

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