Predicting Antibiotic Resistance Evolution through Mechanistic Understanding of Genotype-to-Phenotype Mapping

Imagine an architect, tasked with converting an old football stadium into a building with a different function, without completely demolishing it. While she might contemplate turning the stadium into a housing project, a shopping mall, or an office space, she will not consider turning it into an airport. This is because the existing architecture of a stadium imposes certain constraints: namely, the walls that surround it prevent airplanes from landing. Evolution operates in much the same way as the architect: the existing molecular structures impose constraints that make it more difficult to evolve certain forms compared to others. I study precisely this - how the existing molecular structures shape the likelihood of evolving antibiotic resistance. By identifying those structures that are less likely to evolve resistance, we can better select potential new targets for drugs, so that the time it takes for bacteria to evolve resistance would be prolonged.