Isolated cell behavior drives the evolution of antibiotic resistance

Bacterial antibiotic resistance is typically quantified by the minimum inhibitory concentration (MIC), which is defined as the minimal concentration of antibiotic that inhibits bacterial growth starting from a standard cell density. However, when antibiotic resistance is mediated by degradation, the...

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Bibliographic Details
Main Authors: Artemova, Tatiana, Gerardin, Ylaine, Dudley, Carmel, Vega, Nic, Gore, Jeff
Other Authors: Massachusetts Institute of Technology. Department of Physics
Format: Article
Language:en_US
Published: Nature Publishing Group 2015
Online Access:http://hdl.handle.net/1721.1/98465
https://orcid.org/0000-0003-4583-8555
https://orcid.org/0000-0001-5532-2822
https://orcid.org/0000-0002-9929-6109
Description
Summary:Bacterial antibiotic resistance is typically quantified by the minimum inhibitory concentration (MIC), which is defined as the minimal concentration of antibiotic that inhibits bacterial growth starting from a standard cell density. However, when antibiotic resistance is mediated by degradation, the collective inactivation of antibiotic by the bacterial population can cause the measured MIC to depend strongly on the initial cell density. In cases where this inoculum effect is strong, the relationship between MIC and bacterial fitness in the antibiotic is not well defined. Here, we demonstrate that the resistance of a single, isolated cell—which we call the single‐cell MIC (scMIC)—provides a superior metric for quantifying antibiotic resistance. Unlike the MIC, we find that the scMIC predicts the direction of selection and also specifies the antibiotic concentration at which selection begins to favor new mutants. Understanding the cooperative nature of bacterial growth in antibiotics is therefore essential in predicting the evolution of antibiotic resistance.