Role of AcrAB-TolC and Its Components in Influx–Efflux Dynamics of QAC Drugs in Escherichia coli Revealed Using SHG Spectroscopy,The Journal of Physical Chemistry Letters

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Role of AcrAB-TolC and Its Components in Influx–Efflux Dynamics of QAC Drugs in Escherichia coli Revealed Using SHG Spectroscopy
The Journal of Physical Chemistry Letters ( IF 4.8 ) Pub Date : 2024-07-25 , DOI: 10.1021/acs.jpclett.4c01189
Deepak Singh ₁ , Deepak Kumar ₁ , Anindita Gayen ₁ , Manabendra Chandra _{1,

2}

Affiliation

Multidrug efflux pumps, especially those belonging to the class of resistance-nodulation-division (RND), are the key contributors to the rapidly growing multidrug resistance in Gram-negative bacteria. Understanding the role of efflux pumps in real-time drug transport dynamics across the complex dual-cell membrane envelope of Gram-negative bacteria is thus crucial for developing efficient antibiotics against them. Here, we employ second harmonic generation-based nonlinear spectroscopy to study the role of the tripartite efflux pump and its individual components. We systematically investigate the effect of periplasmic adaptor protein AcrA, inner membrane transporter protein AcrB, and outer membrane channel TolC on the overall drug transport in live Acr-type Escherichia coli and its mutant strain cells. Our results reveal that when one of its components is missing, the tripartite AcrAB-TolC efflux pump machinery in Escherichia coli can effectively function as a bipartite system, a fact that has never been demonstrated in live Gram-negative bacteria.

中文翻译：

使用 SHG 光谱揭示 AcrAB-TolC 及其成分在大肠杆菌中 QAC 药物流入-流出动力学中的作用

多药外排泵，特别是属于耐药结瘤分裂（RND）类的多药外排泵，是革兰氏阴性菌中多药耐药性快速增长的关键因素。因此，了解外排泵在革兰氏阴性菌复杂的双细胞膜包膜上的实时药物转运动力学中的作用对于开发针对它们的有效抗生素至关重要。在这里，我们采用基于二次谐波产生的非线性光谱来研究三方外排泵及其各个组件的作用。我们系统地研究了周质接头蛋白 AcrA、内膜转运蛋白 AcrB 和外膜通道 TolC 对活 Acr 型大肠杆菌及其突变株细胞整体药物转运的影响。我们的结果表明，当其中一个组件缺失时，大肠杆菌中的三联 AcrAB-TolC 外排泵机制可以有效地发挥二联系统的作用，这一事实从未在活革兰氏阴性细菌中得到证实。

更新日期：2024-07-25

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