Sensitive bacterial V m sensors revealed the excitability of bacterial V m and its role in antibiotic tolerance

Sensitive bacterial V m sensors revealed the excitability of bacterial V m and its role in antibiotic tolerance
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敏感的细菌 V m 传感器揭示了细菌 V m 的兴奋性及其在抗生素耐受性中的作用

DOI:
10.1101/2022.06.02.494477
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发表时间:
2022
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通讯作者:
Jin X
Jin X
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作者:
Jin X

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膜电压作为一种重要的自由能源,调节着细菌体内许多重要的生理过程。然而,与真核细胞相比,对细菌电生理的了解非常有限。在这里,我们开发了一套新的基因编码细菌Vmsensors,允许单细胞记录细菌Vmdynamics在活细胞具有高时间分辨率。利用这些新的传感器,我们揭示了细菌细胞的电“兴奋”和“休息”状态取决于它们的代谢状态。在电兴奋状态下,细菌的vare观察到频繁的超极化峰,这是由介质的Na+/K+比例调节的,促进了抗生素耐受性的增加。在电静息状态下,细菌vmv表现出显著的细胞间异质性,并与抗生素治疗后的细胞命运有关。我们的发现证明了我们新开发的电压传感器在揭示细菌vmd和抗生素耐受性之间的基础联系方面的潜力。
As an important free energy source, the membrane voltage (Vm) regulates many essential physiological processes in bacteria. However, in comparison with eukaryotic cells, knowledge of bacterial electrophysiology is very limited. Here, we developed a set of novel genetically encoded bacterial Vmsensors which allow single-cell recording of bacterial Vmdynamics in live cells with high temporal resolution. Using these new sensors, we reveal the electrically “excitable” and “resting” states of bacterial cells dependent on their metabolic status. In the electrically excitable state, frequent hyperpolarization spikes in bacterial Vmare observed, which are regulated by Na+/K+ratio of the medium and facilitate increased antibiotic tolerance. In the electrically resting state, bacterial Vmdisplays significant cell-to-cell heterogeneity and is linked to the cell fate after antibiotic treatment. Our findings demonstrate the potential of our newly developed voltage sensors to reveal the underpinning connections between bacterial Vmand antibiotic tolerance.