Drug detoxification dynamics explain the postantibiotic effect
Abstract The postantibiotic effect (PAE) refers to the temporary suppression of bacterial growth following transient antibiotic treatment. This effect has been observed for decades for a wide variety of antibiotics and microbial species. However, despite empirical observations, a mechanistic underst...
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| Format: | Article |
| Language: | English |
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Springer Nature
2017-10-01
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| Series: | Molecular Systems Biology |
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| Online Access: | https://doi.org/10.15252/msb.20177723 |
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| author | Jaydeep K Srimani Shuqiang Huang Allison J Lopatkin Lingchong You |
| author_facet | Jaydeep K Srimani Shuqiang Huang Allison J Lopatkin Lingchong You |
| author_sort | Jaydeep K Srimani |
| collection | DOAJ |
| description | Abstract The postantibiotic effect (PAE) refers to the temporary suppression of bacterial growth following transient antibiotic treatment. This effect has been observed for decades for a wide variety of antibiotics and microbial species. However, despite empirical observations, a mechanistic understanding of this phenomenon is lacking. Using a combination of modeling and quantitative experiments, we show that the PAE can be explained by the temporal dynamics of drug detoxification in individual cells after an antibiotic is removed from the extracellular environment. These dynamics are dictated by both the export of the antibiotic and the intracellular titration of the antibiotic by its target. This mechanism is generally applicable for antibiotics with different modes of action. We further show that efflux inhibition is effective against certain antibiotic motifs, which may help explain mixed cotreatment success. |
| format | Article |
| id | doaj-art-c1513c283f0347f3b86bfcf1d1bba5fa |
| institution | Kabale University |
| issn | 1744-4292 |
| language | English |
| publishDate | 2017-10-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj-art-c1513c283f0347f3b86bfcf1d1bba5fa2025-08-20T03:46:37ZengSpringer NatureMolecular Systems Biology1744-42922017-10-01131011110.15252/msb.20177723Drug detoxification dynamics explain the postantibiotic effectJaydeep K Srimani0Shuqiang Huang1Allison J Lopatkin2Lingchong You3Department of Biomedical Engineering, Duke UniversityCenter for Synthetic Biology Engineering Research, Shenzhen Institutes of Advanced Technology, Chinese Academy of SciencesDepartment of Biomedical Engineering, Duke UniversityDepartment of Biomedical Engineering, Duke UniversityAbstract The postantibiotic effect (PAE) refers to the temporary suppression of bacterial growth following transient antibiotic treatment. This effect has been observed for decades for a wide variety of antibiotics and microbial species. However, despite empirical observations, a mechanistic understanding of this phenomenon is lacking. Using a combination of modeling and quantitative experiments, we show that the PAE can be explained by the temporal dynamics of drug detoxification in individual cells after an antibiotic is removed from the extracellular environment. These dynamics are dictated by both the export of the antibiotic and the intracellular titration of the antibiotic by its target. This mechanism is generally applicable for antibiotics with different modes of action. We further show that efflux inhibition is effective against certain antibiotic motifs, which may help explain mixed cotreatment success.https://doi.org/10.15252/msb.20177723antibiotic tolerancepostantibiotic effectsystems biology |
| spellingShingle | Jaydeep K Srimani Shuqiang Huang Allison J Lopatkin Lingchong You Drug detoxification dynamics explain the postantibiotic effect Molecular Systems Biology antibiotic tolerance postantibiotic effect systems biology |
| title | Drug detoxification dynamics explain the postantibiotic effect |
| title_full | Drug detoxification dynamics explain the postantibiotic effect |
| title_fullStr | Drug detoxification dynamics explain the postantibiotic effect |
| title_full_unstemmed | Drug detoxification dynamics explain the postantibiotic effect |
| title_short | Drug detoxification dynamics explain the postantibiotic effect |
| title_sort | drug detoxification dynamics explain the postantibiotic effect |
| topic | antibiotic tolerance postantibiotic effect systems biology |
| url | https://doi.org/10.15252/msb.20177723 |
| work_keys_str_mv | AT jaydeepksrimani drugdetoxificationdynamicsexplainthepostantibioticeffect AT shuqianghuang drugdetoxificationdynamicsexplainthepostantibioticeffect AT allisonjlopatkin drugdetoxificationdynamicsexplainthepostantibioticeffect AT lingchongyou drugdetoxificationdynamicsexplainthepostantibioticeffect |