Department of Chemistry & Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556, United States.
Department of Civil & Environmental Engineering & Earth Sciences, University of Notre Dame, Notre Dame, Indiana 46556, United States.
ACS Chem Biol. 2020 May 15;15(5):1184-1194. doi: 10.1021/acschembio.9b00875. Epub 2020 Feb 10.
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 by cohabitating bacteria.
革兰氏阴性菌已经进化出了一种精细的途径来感知和响应β-内酰胺类抗生素的暴露。β-内酰胺类抗生素抑制青霉素结合蛋白,从而使它们的活性丧失/受损,改变细胞壁肽聚糖。细菌感知到这种损伤,并将受影响的肽聚糖去除到复杂的回收途径中。作为这些途径的分支,来自细胞壁回收的肽聚糖化学信号产生了一种 C 类β-内酰胺酶,作为一种耐药机制,该酶将β-内酰胺抗生素水解。我们公开了一种荧光探针的用途,该探针通过检测与信号传导相关的关键肽聚糖的形成来检测回收系统的激活。该探针还可以检测由共生细菌产生的天然产物细胞壁活性抗生素。