Dan Andersson research group

Tempo and mode of bacterial evolution

Our research addresses the mechanisms and dynamics of evolution in bacteria and how various factors such as the extent and type of genetic variation, strength of selection pressures, compensatory mutations and population dynamics affect the tempo and mode of adaptive evolution. Our research is focused on two different areas: 

A) analysis of the various genetic 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 methods, including experimental evolution, bacterial genetics, molecular biology, biochemistry, whole-genome sequencing and mathematical modeling.

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 the extent and type of genetic variation affects bacterial fitness and rates of adaptive evolution.
    
2. Examine the role of gene amplification in adaptive responses (e.g. during exposure to antimicrobial drugs) and in the evolution of novel genes.
    
3. Examine the mechanism, physiological effects and evolutionary constraints on deletion formation. 
    
4. Examine the functional role of ribosomal proteins and define the minimum requirements for an experimentally evolved reduced-size ribosome. 
    
5. Examine the fitness effects and constraints on horizontal gene transfer. 
    
6. Examine the distribution of fitness effects of random mutations and its impact on adaptive evolution.
    

B.Mechanisms and 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 various pathogenic bacteria (e.g. S. typhimurium, E. coli, S. aureus, M. tuberculosis and P. aeruginosa) and which factors determine how rapidly resistance develops in bacterial populations. Our main aims are to:

1. Determine how various types of resistance mechanisms affect bacterial fitness and virulence.
    
2. Determine how bacteria can compensate for resistance-conferred fitness costs. 
    
3. Examine the importance of genetic epistasis on the rate and trajectory of multi-drug-resistance development and compensatory evolution.
    
4. Determine in animal models and human volunteers how antibiotic resistance affects bacterial transmission. 
    
5. Examine the feasibility of reversion of resistance by determining if reduced antibiotic use in community settings may result in a reduced frequency of resistance. 
    
6. Identify mechanisms that confer resistance to antimicrobial peptides and determine the impact of these mechanisms on bacterial fitness and virulence.
    
7. Examine how ultra-low levels of antibiotics affect enrichment and de novo selection for resistant mutants in various types of aquatic environments.