BACKGROUND Thymol is a phenolic compound used for its wide spectrum antimicrobial activity. There is a limited understanding of the antimicrobial mechanisms underlying thymol activity. To investigate this, E. coli strain JM109 was exposed to thymol at sub-lethal concentrations and after 16 rounds of exposure, isolates with a 2-fold increased minimal inhibitory concentration (MIC) were recovered (JM109-Thyr). The phenotype was stable after multiple sub-cultures without thymol. RESULTS Cell morphology studies by scanning electron microscopy (SEM) suggest that thymol renders bacterial cell membranes permeable and disrupts cellular integrity. 1H Nuclear magnetic resonance (NMR) data showed an increase in lactate and the lactic acid family amino acids in the wild type and JM109-Thyr in the presence of thymol, indicating a shift from aerobic respiration to fermentation. Sequencing of JM109-Thyr defined multiple mutations including a stop mutation in the acrR gene resulting in a truncation of the repressor of the AcrAB efflux pump. AcrAB is a multiprotein complex traversing the cytoplasmic and outer membrane, and is involved in antibiotic clearance. CONCLUSIONS Our data suggests that thymol tolerance in E. coli induces morphological, metabolic and genetic changes to adapt to thymol antimicrobial activity.

中文翻译：

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大肠杆菌对百里酚的耐受性会诱导形态，代谢和遗传变化。

背景技术百里香酚是一种酚类化合物，由于其广谱抗菌活性而被使用。对百里酚活性的抗微生物机制了解有限。为了对此进行研究，将大肠杆菌菌株JM109暴露于亚致死浓度的百里酚中，经过16轮暴露后，回收了最低抑制浓度（MIC）增加2倍的分离株（JM109-Thyr）。在没有百里酚的多次传代培养后，该表型是稳定的。结果通过扫描电子显微镜（SEM）进行的细胞形态研究表明，百里香酚使细菌细胞膜具有渗透性并破坏细胞完整性。1H核磁共振（NMR）数据显示，在百里酚存在的情况下，野生型和JM109-Thyr中的乳酸和乳酸家族氨基酸增加，指示从有氧呼吸转变为发酵。JM109-Thyr的测序定义了多个突变，包括acrR基因的终止突变，导致AcrAB外排泵的阻遏物被截短。AcrAB是一种穿越细胞质和外膜的多蛋白复合物，与抗生素清除有关。结论我们的数据表明，大肠杆菌中的百里酚耐受性诱导了形态，代谢和遗传变化，以适应百里酚的抗菌活性。