Linus Sandegren

Professor at Department of Medical Biochemistry and Microbiology; Infection and Immunity; Linus Sandegren

Telephone:
+46 18 471 43 65
E-mail:
Linus.Sandegren@imbim.uu.se
Visiting address:
BMC
Husargatan 3
752 37 UPPSALA
Postal address:
Box 582
751 23 UPPSALA

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Professor Acting deputy at Department of Medical Biochemistry and Microbiology; Administration

E-mail:
linus.sandegren@imbim.uu.se
Visiting address:
BMC
Husargatan 3
752 37 UPPSALA
Postal address:
Box 582
751 23 UPPSALA

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Project Coordinator at Uppsala Antibiotic Center

E-mail:
linus.sandegren@imbim.uu.se
Visiting address:
BMC, SciLifeLab Entrance C11, Room E10:4210
752 37 Uppsala
Postal address:
BMC, Box 582, Husargatan 3
751 23 Uppsala

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Visiting professor at Department of Cell and Molecular Biology; Microbiology and immunology

E-mail:
linus.sandegren@imbim.uu.se
Visiting address:
Husargatan 3
752 37 Uppsala
Postal address:
Box 596
751 24 Uppsala

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Keywords

  • bioinformatics
  • microbiology
  • antibiotic resistance
  • molecular evolution
  • experimental evolution
  • antibiotic
  • bacterial genetics
  • infection biology
  • bacteriology
  • bacterial evolution
  • uppsala antibiotic center

Research

Dynamics of plasmid-borne antibiotic resistance

We study fundamental aspects of how resistance plasmids are maintained and disseminated between pathogenic bacteria and how they serve as platforms for evolution of antibiotic resistance. The main focus is to understand how factors such as stability, mobility, positive selection and fitness cost influence the evolutionary success of plasmids. The experimental systems used are based on clinically isolated multi-resistance plasmids encoding extended spectrum β-lactamases (ESBLs) in enteric bacteria (Escherichia coli and Klebsiella pneumoniae) that pose an increasing clinical problem by providing bacteria with resistance to the most used antibiotics today, β-lactams such as penicillins and cephalosporins.

Four main themes are of particular interest in these studies:

  1. What impact do low levels of antibiotics have on spread, selection and maintenance of multi-resistance plasmids?
  2. What plasmid factors cause a fitness-cost on the host cell and can the fitness-cost of plasmid carriage be alleviated by the bacterium in the absence of antibiotics?
  3. How common are gene amplifications during treatment, how do they affect the efficacy of antibiotics and does the dynamics of gene amplification on plasmids accelerate evolution of new resistance?
  4. How is resistance development and plasmid dynamics influenced by bacterial growth in biofilms compared to planktonic growth?

From these studies we gain new knowledge of how bacterial cells and plasmids co-evolve and how selection of new resistance can accelerate through gene amplification at different antibiotic concentrations. Such knowledge can be used to design antibiotic treatment regimens that limit selection of resistance and minimize the potential for new resistance to evolve.

Linus Sandegren

Publications

Recent publications

All publications

Articles in journal

Articles, review/survey

Conference papers

Manuscripts (preprints)

Reports

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