Dan I. Andersson
Department of Medical Biochemistry and Microbiology, Uppsala
Research: Bacterial adaptation and evolutionOur research is focused on two areas: A) analysis of the various genetic and environmental factors that affect genome stability and variability in bacteria and B) analysis of the factors that influence the dynamics of the evolution of antibiotic resistance development. We study these problems in several bacterial species using a combination of genetics, physiology and experimental evolution.
A. Genome variability and stability. The long-term goal of this project is to examine the major factors that influence the tempo and mode of bacterial evolution. In particular we are interested in the evolutionary and mechanistic factors that influence genome stability and variability. We use the bacterium Salmonella typhimurium as a model system to: 1. Examine how bacteria respond to high mutation rates and how extensive genetic variation affects bacterial fitness. Examine if bacteria have evolved mechanisms that ”buffer” against mutations. 2. Examine the mechanism of adaptive mutability in the lac system. 3. Examine the role of gene amplification in adaptive responses and in the evolution of novel genes. 4. Experimentally evolve a bacterium with a reduced genome. 5. Experimentally evolve a minimal ribosome. 6. Examine how novel functions are incorporated/evolved in a minimal genome.
B. Dynamics of the evolution of antibiotic resistance. The overall objective of this project is to understand how antibiotic resistance affects the fitness, virulence and transmission of bacteria and which factors determine how rapidly resistance develops in a bacterial population. Our main aims are to: 1. Determine how various types of resistance mechanisms affect bacterial fitness. 2. Determine how bacteria can compensate for these fitness costs. 3. Determine how antibiotic resistance affect disease development. 4. Determine in animal models and human volunteers how antibiotic resistance affects bacterial transmission. 5. Determine if reduced antibiotic use in community settings may result in a reduced frequency of resistance. 6. Identify mechanisms that confer resistance to antimicrobial peptides.
Five Selected Publications
DI Andersson, S Slechta and JR Roth (1998) Evidence that gene
amplification underlies adaptive mutability of the bacterial lac operon.
J Björkman, I Nagaev, OG Berg, D Hughes, and DI Andersson (2000) Effects of environment on compensatory mutations to ameliorate the costs of antibiotic resistance.(see Perspectives) Science. 287:1479-1482.
B Björkholm, M Sjölund, M-L Strand, P Falk, L Engstrand, and DI Andersson (2001) Mutation frequency and biological cost of antibiotic resistance in Helicobacter pylori. Proc. Natl. Acad. Sci. USA. 98;14607-14612.
A Nilsson, S Koskiniemi, S Eriksson, E Kugelberg, JCD Hinton and DI Andersson (2005). From the cover: Bacterial genome size reduction by experimental evolution (see Commentary). Proc Natl Acad Sci U S A. 102:12112-12116.
S Maisnier-Patin, JR Roth, Å Fredriksson, T Nyström, OG Berg and DI Andersson (2005) Evidence for antagonistic epistasis between deleterious mutations in a bacterium. Nature Genetics. 37:1376-1379.