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Following evolution of bacterial antibiotic resistance in real time

Nature Genetics volume 44, pages 11–13 (2012)Cite this article

A new study reports the development of the 'morbidostat', a device that allows for continuous culture of bacteria under a constant drug selection pressure using computer feedback control of antibiotic concentration. This device, together with bacterial whole-genome sequencing, allowed the authors to follow the evolution of resistance-conferring mutations in Escherichia coli populations in real time, providing support for deterministic evolution of resistance in some situations.

Microorganisms can and do evolve resistance to antibiotics. In recent decades, the spread of bacterial drug resistance has been accelerated by the widespread use of antibiotics in agriculture and in healthcare. This trend has raised fundamental and urgent questions about the dynamics and genetic basis of bacterial resistance. What specific mutations arise in response to low drug concentrations, and how do additional mutations strengthen resistance at higher drug concentrations? Does resistance result from mutations in just one or a few genes, or is it spread more broadly across the genome? Finally, to what extent are the specific mutations that confer antibiotic resistance and the temporal sequence in which they arise predictable? Addressing these questions requires the ability to map mutations at a genome-wide scale and to do so over time during a continuous evolutionary process. On page 101 of this issue, Roy Kishony and colleagues1 achieve such real-time measurements by combining whole-genome sequencing with a new, powerful feedback system for continuous cultivation of bacteria under constant selection pressure. This technical advance in laboratory-based evolution is beginning to answer many of these questions.

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Figure 1: The morbidostat applies a continuous selective pressure to the bacterial population.

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  1. Division of Biology, Adam Z. Rosenthal and Michael B. Elowitz are at the Howard Hughes Medical Institute, California Institute of Technology, Pasadena, California, USA.,

    Adam Z Rosenthal & Michael B Elowitz

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  1. Adam Z Rosenthal
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  2. Michael B Elowitz
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Correspondence to Michael B Elowitz.

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The authors declare no competing financial interests.

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Rosenthal, A., Elowitz, M. Following evolution of bacterial antibiotic resistance in real time. Nat Genet 44, 11–13 (2012). https://doi.org/10.1038/ng.1048

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