Fluorescence Assessment of the AmpR-Signaling Network of Pseudomonas aeruginosa to Exposure to β-Lactam Antibiotics.,ACS Chemical Biology

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Fluorescence Assessment of the AmpR-Signaling Network of Pseudomonas aeruginosa to Exposure to β-Lactam Antibiotics.
ACS Chemical Biology ( IF 3.5 ) Pub Date : 2020-02-10 , DOI: 10.1021/acschembio.9b00875
David A Dik ₁ , Choon Kim ₁ , Chinedu S Madukoma ₂ , Jed F Fisher ₁ , Joshua D Shrout _{2,

3} , Shahriar Mobashery ₁

Affiliation

Gram-negative bacteria have evolved an elaborate pathway to sense and respond to exposure to β-lactam antibiotics. The β-lactam antibiotics inhibit penicillin-binding proteins, whereby the loss of their activities alters/damages the cell-wall peptidoglycan. Bacteria sense this damage and remove the affected peptidoglycan into complex recycling pathways. As an offshoot of these pathways, muropeptide chemical signals generated from the cell-wall recycling manifest the production of a class C β-lactamase, which hydrolytically degrades the β-lactam antibiotic as a resistance mechanism. We disclose the use of a fluorescence probe that detects the activation of the recycling system by the formation of the key muropeptides involved in signaling. This same probe additionally detects natural-product cell-wall-active antibiotics that are produced in situ by cohabitating bacteria.

中文翻译：

铜绿假单胞菌AmpR信号网络暴露于β-内酰胺抗生素的荧光评估。

革兰氏阴性细菌已发展出一条复杂的途径来感知和响应暴露于β-内酰胺类抗生素。β-内酰胺抗生素会抑制青霉素结合蛋白，从而丧失其活性，从而改变/损坏细胞壁肽聚糖。细菌感觉到这种损害并将受影响的肽聚糖清除到复杂的回收途径中。作为这些途径的分支，从细胞壁回收产生的多肽化学信号表明产生了C类β-内酰胺酶，该酶水解降解了β-内酰胺抗生素，成为一种耐药机制。我们公开了荧光探针的使用，该荧光探针通过参与信号传导的关键多聚肽的形成来检测回收系统的激活。

更新日期：2020-01-28

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