Isolated cell behavior drives the evolution of antibiotic resistance

Abstract 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 degrada...

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Main Authors: Tatiana Artemova, Ylaine Gerardin, Carmel Dudley, Nicole M Vega, Jeff Gore
Format: Article
Language:English
Published: Springer Nature 2015-07-01
Series:Molecular Systems Biology
Subjects:
Online Access:https://doi.org/10.15252/msb.20145888
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author Tatiana Artemova
Ylaine Gerardin
Carmel Dudley
Nicole M Vega
Jeff Gore
author_facet Tatiana Artemova
Ylaine Gerardin
Carmel Dudley
Nicole M Vega
Jeff Gore
author_sort Tatiana Artemova
collection DOAJ
description Abstract 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.
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institution Kabale University
issn 1744-4292
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spelling doaj-art-568a3ca8574e494db8250f3afd2964f72025-08-20T03:46:32ZengSpringer NatureMolecular Systems Biology1744-42922015-07-0111711110.15252/msb.20145888Isolated cell behavior drives the evolution of antibiotic resistanceTatiana Artemova0Ylaine Gerardin1Carmel Dudley2Nicole M Vega3Jeff Gore4Department of Physics, Massachusetts Institute of TechnologyDepartment of Systems Biology, Harvard Medical SchoolDepartment of Physics, Massachusetts Institute of TechnologyDepartment of Physics, Massachusetts Institute of TechnologyDepartment of Physics, Massachusetts Institute of TechnologyAbstract 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.https://doi.org/10.15252/msb.20145888antibiotic resistancebeta‐lactamasecooperative growthevolution
spellingShingle Tatiana Artemova
Ylaine Gerardin
Carmel Dudley
Nicole M Vega
Jeff Gore
Isolated cell behavior drives the evolution of antibiotic resistance
Molecular Systems Biology
antibiotic resistance
beta‐lactamase
cooperative growth
evolution
title Isolated cell behavior drives the evolution of antibiotic resistance
title_full Isolated cell behavior drives the evolution of antibiotic resistance
title_fullStr Isolated cell behavior drives the evolution of antibiotic resistance
title_full_unstemmed Isolated cell behavior drives the evolution of antibiotic resistance
title_short Isolated cell behavior drives the evolution of antibiotic resistance
title_sort isolated cell behavior drives the evolution of antibiotic resistance
topic antibiotic resistance
beta‐lactamase
cooperative growth
evolution
url https://doi.org/10.15252/msb.20145888
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AT ylainegerardin isolatedcellbehaviordrivestheevolutionofantibioticresistance
AT carmeldudley isolatedcellbehaviordrivestheevolutionofantibioticresistance
AT nicolemvega isolatedcellbehaviordrivestheevolutionofantibioticresistance
AT jeffgore isolatedcellbehaviordrivestheevolutionofantibioticresistance