Evolution of pathogenic bacteria

Our team explores the evolution of Salmonella Typhimurium and the role of variability during infection.

Salmonella Typhimurium. Photo credit: Fattinger S, Sellin M and Hardt WD, with the help of ETH ScopeM.

The current antibiotic resistance crisis testifies that technological progress is lagging behind bacterial evolution. Understanding the general principles underlying the evolution of pathogens will be essential to design strategies shifting away from classical approaches that rely almost entirely on antimicrobial chemotherapy.

Individuality and division of labor in pathogen communities
Bacterial populations are generally complex communities of phenotypically diverse individuals. This diversity originates from several sources including random variations in gene expression. This means that genetically identical cells can express different phenotypes even in a constant and homogeneous environment. We are exploring the molecular mechanisms and evolutionary bases of this phenomenon in Salmonella Typhimurium. Our working hypothesis is that this allows the pathogen to divide labor between subpopulations of cells in the gut in order to maximize transmission of virulent genotypes to the next host.

The role of transmission in pathogens evolution
Transmitting from donor to recipient hosts is a key step in the life cycle of every pathogen. Using next generation sequencing technologies, we are quantitatively addressing the population dynamics and evolvability of S. Typhimurium during both long-term within-host infection and host-to-host transmission. The impact of factors that limit these different steps in the pathogen life-cycle are experimentally investigated. These factors include the intestinal microbiota and the host immunity.   

Designing robust biocontrol strategies
The knowledge accumulated on the genetic basis of virulence, on the within-host evolution of S. Typhimurium, and further advances on the transmission dynamics will be combined to design preventive strategies that will exclude virulent strains from populations of hosts and prohibit the emergence of mutants able to escape the treatment.