Department of Biomedical Engineering, Duke University, Durham, NC, USA.
Center for Synthetic Biology Engineering Research, Shenzhen Institutes of Advanced Technology Chinese Academy of Sciences, Shenzhen, China.
Mol Syst Biol. 2017 Oct 23;13(10):948. doi: 10.15252/msb.20177723.
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.
抗生素后效应（PAE）是指在短暂的抗生素治疗后对细菌生长的暂时抑制。几十年来，人们已经观察到各种抗生素和微生物物种都存在这种效应。然而，尽管有经验观察，但人们对这种现象的机制理解还很缺乏。我们使用建模和定量实验相结合的方法，表明抗生素从细胞外环境中去除后，药物在单个细胞中的解毒的时间动态可以解释 PAE。这些动态受到抗生素的外排和抗生素靶标的细胞内滴定的共同控制。这种机制通常适用于具有不同作用模式的抗生素。我们还进一步表明，外排抑制对某些抗生素基序有效，这可能有助于解释混合联合治疗的成功。
