The role of plasmids in bacterial adaptation

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Plasmids play a key role in bacterial evolution. In particular, they can carry antibiotic resistance genes, making these genes highly mobile and allowing them to cross species boundaries. Although clinically relevant resistance is often encoded on plasmids, the majority of theoretical models focuses on chromosomal resistance. In order to close this gap, I will develop mathematical models to address two major open questions - the evolutionary potential of multicopy plasmids (Projects 1 and 2) and the role of commensal bacteria as a reservoir of resistance genes that can be picked up by pathogens (Project 3). Existing models incorporating plasmid-borne resistance are usually based on deterministic differential equations, similar to epidemiological models (with the plasmid taking the role of the parasite). In contrast, we will mainly use stochastic approaches, following the modeling framework from population genetics models of evolutionary rescue. Major parts of the analysis will be based on branching process theory. Analytical approximations of the stochastic process will be complemented by the analysis of deterministic differential equations and by stochastic computer simulations.In Project 4, we will turn away from drug resistance and explore the effect of plasmidmediated conjugation on chromosomal adaptation. The goal is to assess up to which extent it is justified to call conjugation a form of "bacterial sex", a question that has only marginally been addressed in theoretical studies so far. To this purpose, we will set up population genetics models analogous to those used to describe recombination during sexual reproduction and compare the results.