A lux-based Staphylococcus aureus bioluminescence screening assay for the detection/identification of antibiotics and prediction of antibiotic mechanisms
A lux-based Staphylococcus aureus bioluminescence screening assay for the detection/identification of antibiotics and prediction of antibiotic mechanisms
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DOI：
10.1038/s41429-020-0349-7
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发表时间：
2020-07
期刊：
影响因子：
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通讯作者：
Zhongjun Yang;Qingyu Cui;Mengge Zhang;Zhiqiang Li;Mingyu Wang;Hai Xu
中科院分区：
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作者：
Zhongjun Yang;Qingyu Cui;Mengge Zhang;Zhiqiang Li;Mingyu Wang;Hai Xu
发现新抗生素和解决抗生素耐药性问题的需要需要快速检测抗生素、鉴定已知抗生素和预测抗生素机制。细菌lux基因编码的蛋白质将化学能转化为光子能，并导致生物发光。利用这一现象，我们构建了一个基于LUX的生物发光系统，在金黄色葡萄球菌中表达应激诱导型伴侣启动子控制下的LUX基因。当经历抗生素胁迫时，这些构建的报告菌株显示出明显的生物发光反应。因此，该生物发光筛选系统可用于未知化学混合物中抗生素的检测。对生物发光响应模式的进一步分析表明：（1）这些生物发光响应模式具有高度抗生素特异性，因此可用于快速和廉价的抗生素鉴定;（2）具有相同作用机制的抗生素具有相似的生物发光模式，因此这些模式可用于预测未知抗生素的机制，具有良好的灵敏度和特异性。利用生物发光筛选技术，可以促进新抗生素的发现和分析，有利于解决抗生素耐药性问题。
The need for the discovery of new antibiotics and solving the antibiotic resistance problem requires rapid detection of antibiotics, identification of known antibiotics, and prediction of antibiotic mechanisms. The bacterial lux genes encode proteins that convert chemical energy into photonic energy and lead to bioluminescence. Exploiting this phenomenon, we constructed a lux-based bioluminescence system in Staphylococcus aureus by expressing lux genes under the control of stress-inducible chaperon promoters. When experiencing antibiotic stress, these constructed reporter strains showed clear bioluminescence response. Therefore, this bioluminescence screening system can be used for the detection of antibiotics in unknown chemical mixtures. Further analysis of bioluminescence response patterns showed that: (1) these bioluminescence response patterns are highly antibiotic specific and therefore can be used for rapid and cheap identification of antibiotics; and that (2) antibiotics having the same mechanism of action have similar bioluminescence patterns and therefore these patterns can be used for the prediction of mechanism for an unknown antibiotic with good sensitivity and specificity. With this bioluminescence screening assay, the discovery and analysis of new antibiotics can be promoted, which benefits in solving the antibiotic resistance problem.