Microbial Pharmacology and Population Biology (MicroPop)

From the left: Department engineer Francois Pierre Alexandre Cléon, Masterstudent Angie Carola Alarcon Rios, Department engineer Mikkel Meyn Liljegren, Medical research student Anna Sollied Møller, Biostatistician Joachim Hegstad, Doctoral Research Fellow Julia Maria Kloos, Professor and Group leader Pål Jarle Johnsen, Doctoral Research Fellow Jonina Gudmundsdottir, Researcher Klaus Harms, Associate Professor Elizabeth G. Aarag Fredheim, Professor Ørjan Samuelsen, Project coordinator Maria-Elena Putz, Postdoctoral fellow Joao Pedro Alves Gama. Not present: Associate Professor Raul Primicerio, Postdoctoral fellow Vidar Sørum, Postdoctoral fellow Nicole L. Podnecky, Medical research student Emma Lu Øyenes.

MicroPop focus 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 and the transmission dynamics of antimicrobial resistance genes/elements in bacterial populations.

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 how it affects genetic diversity in microbes.

Selected Publications:

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. Available at Preprints with THE Lancet: SSRN: https://dx.doi.org/10.2139/ssrn.3645193  (In press, Lancet Microbe)

Kloos J., Gama JA., Hegstad J., Samuelsen Ø., PJ. Johnsen, Piggybacking on Niche Adaptation Improves the Maintenance of Multidrug‐Resistance Plasmids, Molecular Biology and Evolution, 2021;  msab091, https://doi.org/10.1093/molbev/msab091

Podnecky NL, Fredheim EGA,, Kloos J, Sørum V, Primicerio R, Roberts AP, Rozen DE, Samuelsen Ø, PJ Johnsen. Conserved collateral antibiotic susceptibility networks in diverse clinical strains of Escherichia coli. Nat. Commun. 2018; 9: 3673

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. 2017 Jan;72(1):85-89. 

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 15066-071

Engelstädter J., Harms K., Johnsen PJ. The evolutionary dynamics of integrons in changing environments ISME J, 2016, Jun;10(6):1296-307.

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

Utnes A., Sorum V., Hulter N., Primicerio R., Kloos J., Nielsen K.M., andP. J. 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

Levin B. R., Baquero F., and P. J. Johnsen. A Model-Guided Analysis and Perspective on the Evolution and Epidemiology of Antibiotic Resistance and its Future. 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.,  and P. J. Johnsen. * 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.

StarikovaI., Harms K., Lunde T. M., Haugen P., Primicerio R., Samuelsen Ø., Nielsen K. M, and P. J. Johnsen. 2012. A trade-off between the fitness cost of functional integrases and long-term stability of integrons. PloS Pathog.8(11):e1003043.

Group members:

Pål J. Johnsen, Professor and group leader

Raul Primicerio, Associate Professor

Ørjan Samuelsen, Professor (20%) and Norwegian National Advisory Unit on Detection of Antimicrobial Resistance, University Hospital of North Norway.

Elizabeth Aarag Fredheim, Associate Professor

Nicole Podnecky, Postdoctoral Fellow

João Pedro Alves Gama, Postdoctoral fellow

Klaus Harms, Researcher/Research associate

Vidar Sørum, Postdoctoral Fellow

Julia Kloos, PhD student

Jónína Gudmundsdóttir, PhD student

Mikkel Meyn Liljegren, Lab Manager

François Pierre Alexandre Cléon, Lab Manager

Anna Sollied Møller, Medical Student Research Programme

Emma Lu Øynes, Medical Student Research Programme

Maria-Elena Putz, Project coordinator

Former Group Members:

Dr. Nils Hülter

Dr. Irina Starikova

Dr. Ane Utnes

Dr. Maria Chiara de Luca

Jessica N. Tran, MSc

Kristina B. Pedersen, MSc

Asbjørn Lunnan, MSc

Lilli Nguyen, MSc

Jonathan Nguyen, MSc

Gina Pat, MSc

Mari Norvik, MSc

Joachim Hegstad, MSc

Tammy Nguyen, MSc

Cho Kit Lam, MSc

Sanne E. Valla, MSc

Camilla R. Hasund, MSc 

Annika Koumans, Erasmus+ student

Marie Hella Lindberg, Project coordinator 

Christopher Fröhlich, Erasmus+ student

Chantal Verstappen, Erasmus+ student

Tracy T. M. Lunde, PhD student