The importance of evolutionary reservoirs for pathogen emergence

An experimental test of the theoretical predictions with a Caenorhabditis elegans-pathogen model system

Microbial parasites are ubiquitous and infect all living beings. Recent advances in theoretical epidemiology highlight the role of immunodeficient hosts as incubators for novel pathogen strains. However, none of the predictions has been tested experimentally. I am investigating these hypotheses using C. elegans worms as a model system. This nematode possesses naturally developed physiological defense mechanisms against pathogens, and offers an exceptional opportunity to study the evolutionary context of pathogen adaptation. My studies integrate evolutionary biology with molecular biology, epidemiology and medicine through the use of experimental evolution. I use four C. elegans host strains: the wild-type N2 strain and three mutant lines for which one immunity pathway has been compromised: the p38-mitogen activated pathway (TIR-1 knock-out), the Insuline-like receptor pathway (DAF-16 knock-out) and the TGF-ß pathway (reduced-function DBL-1). I infect these four host strains with several bacterial pathogens which have been chosen because (i) they are only distantly related to each other (thus increasing the generality of my results), (ii) they represent very different virulence mechanisms, (iii) they are known to infect C. elegans and co-occur with the host in natural conditions and (iv) some are opportunistic human pathogens, which may enable me to generalize results to human pathology. I thus chose Serratia marcescens, Bacillus thuringiensis, Pseudomonas aeruginosa and Staphylococcus aureus. I will compare the evolutionary outcomes across the pathogen species and the types of C. elegans immunodeficiency. After experimental evolution and phenotypic tests on the evolved strains, I will reconstruct the underlying genetics of virulence evolution by genetic/sequence analysis, including but not limited to whole-genome sequencing, expression analysis, candidate gene analysis, and population genetics/phylogenetics at different time points. I aim to understand the temporal dynamics and genetics of pathogen emergence and virulence evolution within immunocompromised hosts.

Involved people: Gunther Jansen, Felix Gilbert, Robert Thänert, Hinrich Schulenburg

Collaborators: Jamie Lloyd-Smith, Los Angeles, US; Philip Rosenstiel, Kiel, Germany

Funding: VW foundation