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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| Format: | Article |
| Language: | en_US |
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Nature Publishing Group
2015
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| 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 |
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| author | Artemova, Tatiana Gerardin, Ylaine Dudley, Carmel Vega, Nic Gore, Jeff |
| author2 | Massachusetts Institute of Technology. Department of Physics |
| author_facet | Massachusetts Institute of Technology. Department of Physics Artemova, Tatiana Gerardin, Ylaine Dudley, Carmel Vega, Nic Gore, Jeff |
| author_sort | Artemova, Tatiana |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T11:28:03Z |
| format | Article |
| id | mit-1721.1/98465 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T11:28:03Z |
| publishDate | 2015 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/984652022-10-01T03:48:55Z Isolated cell behavior drives the evolution of antibiotic resistance Artemova, Tatiana Gerardin, Ylaine Dudley, Carmel Vega, Nic Gore, Jeff Massachusetts Institute of Technology. Department of Physics Artemova, Tatiana Dudley, Carmel Vega, Nic Gore, Jeff 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. National Institutes of Health (U.S.) (R01GM102311-01) National Institutes of Health (U.S.) (R00 Pathways to Independence GM085279-02) National Science Foundation (U.S.) (CAREER PHY-1055154) Alfred P. Sloan Foundation (Fellowship BR2011-066) Paul Allen Foundation (Distinguished Investigator Program) National Institutes of Health (U.S.) (New Innovator DP2) Pew Charitable Trusts (Pew Scholars Program in Biomedical Sciences 2010-000224-007) 2015-09-11T16:44:45Z 2015-09-11T16:44:45Z 2015-07 Article http://purl.org/eprint/type/JournalArticle 1744-4292 http://hdl.handle.net/1721.1/98465 Artemova, T., Y. Gerardin, C. Dudley, N. M. Vega, and J. Gore. “Isolated Cell Behavior Drives the Evolution of Antibiotic Resistance.” Molecular Systems Biology 11, no. 7 (July 1, 2015): 822–822. https://orcid.org/0000-0003-4583-8555 https://orcid.org/0000-0001-5532-2822 https://orcid.org/0000-0002-9929-6109 en_US http://dx.doi.org/10.15252/msb.20145888 Molecular Systems Biology Creative Commons Attribution http://creativecommons.org/licenses/by/4.0/ application/pdf Nature Publishing Group Nature Publishing Group |
| spellingShingle | Artemova, Tatiana Gerardin, Ylaine Dudley, Carmel Vega, Nic Gore, Jeff Isolated cell behavior drives the evolution of antibiotic resistance |
| 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 |
| url | 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 |
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