Drug detoxification dynamics explain the postantibiotic effect |
| |
| Authors: | Jaydeep K Srimani Shuqiang Huang Allison J Lopatkin Lingchong You |
| |
| Affiliation: | 1. Department of Biomedical Engineering, Duke University, Durham, NC, USA;2. Center for Synthetic Biology Engineering Research, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China;3. Center for Genomic and Computational Biology, Duke University, Durham, NC, USA;4. Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC, USA |
| |
| 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. |
| |
| Keywords: | antibiotic tolerance postantibiotic effect systems biology |
|
|
