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Antibiotic Resistance, Not Shaken or Stirred

James Bond preferred vodka martinis shaken, not stirred, displaying impressive discriminatory power. Bacteria may be similarly discerning. Zhang et al. (1) abandoned the standard lab practice of growing bacteria in shaking homogeneous liquid cultures in favor of fabricated microenvironments and report, on page 1764 of this issue, that bacteria can tell the difference. They evolve antibiotic resistance far more rapidly in the structured environment. Evolution seems to work differently in the microenvironment, and perhaps more like evolution in the real world.

In the human body, bacteria encounter heterogeneous environments full of transient chemical and nutrient gradients. Antibiotic gradients can arise when a patient begins and ends therapies, or forgets doses. They might form across spatial heterogeneities as well. For example, the concentration of an antibiotic may be high in blood but low in less permeable dense bacterial clumps or biofilms. To simulate real-world conditions, Zhang et al. built a microfluidic device of tiny chambers to create gradients of both a specific chemical and nutrients. The authors then assessed the effect of the microenvironments generated within these chambers on bacterial populations grown in them. This approach may more accurately reflect encounters of microorganisms with chemicals and nutrients in the heterogeneous range of niches they encounter in the real world, such as in soil or within an animal's body. They found that when bacteria (Escherichia coli) are grown in a heterogeneous environment that includes a steep concentration gradient of the antibiotic ciprofloxacin (cipro), they show surprisingly rapid and repeatable acquisition and fixation of cipro-resistance mutations compared with bacteria in homogeneous environments.

Science 23 September 2011:
Vol. 333 no. 6050 pp. 1713-1714
DOI: 10.1126/science.1212449

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