Antibiotikaresistens

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Telefon: 77623156
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

Forskningsinteresser:

Prosesser (horisontal genoverføring) og effekter knyttet til bakteriell ervervelse av resistens til antimikrobielle legemidler. Biosikkerhetsforskning. 


Telefon: 77644070
Forskningsinteresser:
  • Makromolekylers struktur og funksjon
  • Det molekylære opphav til enzymers kuldeadaptasjon
  • Utvikling av enzymer for anvendelse
  • Bioprospektering

Telefon: 77645792
Forskningsinteresser:

Legemiddelbruk på individ- og populasjonsnivå, med hovedfokus på antibiotikabruk.


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