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引用次数: 0
摘要
抗生素的发现极大地促进了人类文明的发展,然而,滥用和过度使用抗生素所导致的细菌耐药性却极大地挑战着人类健康和食品安全。面对日益严峻的形势,人们迫切要求开发新兴的非传统技术或方法来解决这一问题。随着合成生物学的发展,光遗传学在许多领域的基因表达精确调控方面展现出诱人的前景。因此,利用光遗传学来降低抗生素耐药性的风险很有吸引力。本文基于一种光敏 DNA 结合蛋白(EL222),在大肠杆菌中建立了一种蓝光可控基因表达系统。此外,还利用蓝光成功抑制了β-内酰胺酶基因(bla)的表达,从而大大降低了工程大肠杆菌对氨苄西林的耐药性。此外,利用蓝光诱导大电导机械敏感通道(MscL)的表达,成功地提高了工程大肠杆菌对链霉素的敏感性。最后,在同一个大肠杆菌细胞中,蓝光同时诱导氨苄西林和链霉素敏感性的增加,揭示了这一策略在控制耐多药(MDR)细菌方面的巨大潜力。作为概念验证,我们的工作证明了光可以作为一种替代工具,在不开发新抗生素的情况下延长普通抗生素的使用期。这种基于光遗传学的新策略为未来抗击抗生素耐药性开辟了前景广阔的道路。
Blue light-mediated gene expression as a promising strategy to reduce antibiotic resistance in Escherichia coli
The discovery of antibiotics has noticeably promoted the development of human civilization; however, antibiotic resistance in bacteria caused by abusing and overusing greatly challenges human health and food safety. Considering the worsening situation, it is an urgent demand to develop emerging nontraditional technologies or methods to address this issue. With the expanding of synthetic biology, optogenetics exhibits a tempting prospect for precisely regulating gene expression in many fields. Consequently, it is attractive to employ optogenetics to reduce the risk of antibiotic resistance. Here, a blue light-controllable gene expression system was established in Escherichia coli based on a photosensitive DNA-binding protein (EL222). Further, this strategy was successfully applied to repress the expression of β-lactamase gene (bla) using blue light illumination, resulting a dramatic reduction of ampicillin resistance in engineered E. coli. Moreover, blue light was utilized to induce the expression of the mechanosensitive channel of large conductance (MscL), triumphantly leading to the increase of streptomycin susceptibility in engineered E. coli. Finally, the increased susceptibility of ampicillin and streptomycin was simultaneously induced by blue light in the same E. coli cell, revealing the excellent potential of this strategy in controlling multidrug-resistant (MDR) bacteria. As a proof of concept, our work demonstrates that light can be used as an alternative tool to prolong the use period of common antibiotics without developing new antibiotics. And this novel strategy based on optogenetics shows a promising foreground to combat antibiotic resistance in the future.
Biotechnology JournalBiochemistry, Genetics and Molecular Biology-Molecular Medicine
CiteScore
8.90
自引率
2.10%
发文量
123
审稿时长
1.5 months
期刊介绍:
Biotechnology Journal (2019 Journal Citation Reports: 3.543) is fully comprehensive in its scope and publishes strictly peer-reviewed papers covering novel aspects and methods in all areas of biotechnology. Some issues are devoted to a special topic, providing the latest information on the most crucial areas of research and technological advances.
In addition to these special issues, the journal welcomes unsolicited submissions for primary research articles, such as Research Articles, Rapid Communications and Biotech Methods. BTJ also welcomes proposals of Review Articles - please send in a brief outline of the article and the senior author''s CV to the editorial office.
BTJ promotes a special emphasis on:
Systems Biotechnology
Synthetic Biology and Metabolic Engineering
Nanobiotechnology and Biomaterials
Tissue engineering, Regenerative Medicine and Stem cells
Gene Editing, Gene therapy and Immunotherapy
Omics technologies
Industrial Biotechnology, Biopharmaceuticals and Biocatalysis
Bioprocess engineering and Downstream processing
Plant Biotechnology
Biosafety, Biotech Ethics, Science Communication
Methods and Advances.