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The evolution of antibiotic resistance, on a plate

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Researchers have developed a large culturing device to track the evolution of bacteria as they mutate in the presence of antibiotics, revealing that, surprisingly, the fittest mutants were not those most likely to infiltrate higher antibiotic concentrations. Instead, bacteria "behind" the very fittest on the growth plate became capable of surviving at highest antibiotic concentrations. The results provide important insights into the evolutionary patterns and mechanisms that drive bacteria's success in overcoming antibiotics, a phenomenon that threatens human health worldwide. To better understand the emergence of antibiotic resistance in space and time, Michael Baym and colleagues developed a device called the microbial evolution growth arena plate, or MEGA plate – a large, rectangular petri dish across which different concentrations of antibiotics can be applied; here, the researchers used trimethoprim and ciprofloxacin. Bacteria were cultured at one location on the plate; as competition for resources increased, they spread to other regions. Applying varying levels of antibiotics, the authors were able to map out mutations that allowed increasingly resistant mutant bacteria to spread. Bacteria were unable to adapt directly from zero antibiotic to the highest concentrations, for both drugs tested, revealing that exposure to intermediate concentrations of antibiotics is essential for the bacteria to evolve resistance. Mutations that increased resistance often came at the cost of reduced growth, which was subsequently restored by additional compensatory mutations, the authors found. Intriguingly, the spatial location of bacterial species played a role in their success in developing resistance. For example, when the researchers moved the trapped mutants (those behind their "fit" parents) to the "frontlines" of the culture, they were able to grow into new regions where the frontline bacteria could not. In light of this finding, the authors suggest that the fitness of bacterial populations is not driven by the fittest mutants, but rather by those that are both sufficiently fit and arise sufficiently close to the advancing front. As Luke McNally and Sam Brown explain in a related Perspective, the MEGA plate device developed here, which provided "an unprecedented visualization of [bacterial] evolution through time and space," could be used to explore additional aspects of drug resistance evolution.

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