Collaborative Research: Adaptive Bridge or Barrier? The Impact of Horizontal Transfer on Genetic Evolution

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Bacteria are an essential part of life on earth, but we do not really understand how they rapidly adapt to new environments. Genes in bacteria are not only inherited from parent to offspring but can also transfer between different species. This “horizontal gene transfer” is often caused by small genetic elements called conjugative plasmids. These plasmids carry the machinery to move copies of themselves into new bacterial cells. A gene on one of these plasmids can inhabit very different host cells over time. A mutation in this gene may then have different effects in each host. This means genes could evolve differently during parent offspring transmission than when they are transferred horizontally between species. This project combines mathematical models and experiments with different bacterial species to measure the effect of horizontal transfer on the evolution of an antibiotic resistance gene and determine how that influences adaptation to changing conditions. Because antibiotic resistance genes are often located on these plasmids, this will aid in combating the evolution of drug resistance. Additional broader impacts include the development of learning tools and a new undergraduate course that will provide authentic research experiences for students. This project has three research aims. First, the researchers will propagate communities with combinations of three bacterial species (Escherichia coli, Salmonella enterica, and Klebsiella pneumoniae) and monitor the evolution of a plasmid-borne gene coding for resistance to beta-lactam antibiotics. Horizontal gene transfer will be manipulated during this process to determine the role of transfer between species in evolution of drug resistance. Second, genetically engineered bacteria will be used to determine why certain mutational sets are favored during horizontal transfer. Mathematically modeling of the results will produce predictions about whether horizontal transfer speeds or hinders the evolution of drug resistance. Third, the researchers will build a computational model to incorporate more realistic features of microbial communities, including more complex environments, migration, and competition between different bacterial species. This model will be tested in live bacterial communities with horizontal transfer turned on or off through plasmid engineering. Overall, this project will elucidate the role that horizontal genetic inheritance plays in the evolution of bacterial communities.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.