Real-Time Monitoring of Multitarget Antimicrobial Mechanisms of Peptoids Using Label-Free Imaging with Optical Diffraction Tomography.
Real-Time Monitoring of Multitarget Antimicrobial Mechanisms of Peptoids Using Label-Free Imaging with Optical Diffraction Tomography.
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DOI：
10.1002/advs.202302483
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发表时间：
2023-08
期刊：
影响因子：
15.1
通讯作者：
Seo, Jiwon
中科院分区：
文献类型：
--
作者：
Kim, Minsang;Cheon, Yeongmi;Shin, Dongmin;Choi, Jieun;Nielsen, Josefine Eilso;Jeong, Myeong Seon;Nam, Ho Yeon;Kim, Sung-Hak;Lund, Reidar;Jenssen, Havard;Barron, Annelise E.;Lee, Seongsoo;Seo, Jiwon
抗菌肽（AMP）是对抗多重耐药细菌的有前途的治疗药物。作为AMP的模拟物，具有N-取代的甘氨酸骨架的类肽已被用于对蛋白水解降解具有抗性的抗微生物剂。已知抗微生物类肽通过膜破坏杀死细菌;然而，细胞内内容物的非特异性聚集也被认为是重要的杀菌机制。在这里，研究了含有吲哚侧链的类肽文库的结构-活性关系（SAR），从而产生作为命中化合物的类肽29。然后，使用光学衍射断层扫描（ODT）以无标记方式对用AMP和类肽29处理的活细菌进行定量形态学分析。通过监测细菌的真实的时间形态变化，明确证明了膜破坏和细胞内生物质絮凝是细菌杀灭的主要机制。这些多靶点机制和快速作用可能是发现破坏耐药性的新型抗生素药物的优点。使用ODT以无标记的方式对用蜂毒肽、buforin-II和命中类肽（29）处理的活细菌进行定量形态学分析。利用抗微生物类肽29，通过真实的-时间ODT成像明确地证明了膜破坏和细胞内生物质絮凝是细菌杀灭的主要机制。
Antimicrobial peptides (AMPs) are promising therapeutics in the fight against multidrug‐resistant bacteria. As a mimic of AMPs, peptoids with N‐substituted glycine backbone have been utilized for antimicrobials with resistance against proteolytic degradation. Antimicrobial peptoids are known to kill bacteria by membrane disruption; however, the nonspecific aggregation of intracellular contents is also suggested as an important bactericidal mechanism. Here,structure‐activity relationship (SAR) of a library of indole side chain‐containing peptoids resulting in peptoid 29 as a hit compound is investigated. Then, quantitative morphological analyses of live bacteria treated with AMPs and peptoid 29 in a label‐free manner using optical diffraction tomography (ODT) are performed. It is unambiguously demonstrated that both membrane disruption and intracellular biomass flocculation are primary mechanisms of bacterial killing by monitoring real‐time morphological changes of bacteria. These multitarget mechanisms and rapid action can be a merit for the discovery of a resistance‐breaking novel antibiotic drug. Quantitative morphological analyses of live bacteria treated with melittin, buforin‐II, and hit peptoid (29) in a label‐free manner using ODT) are performed. With antimicrobial peptoid 29, it is unambiguously demonstrated that both membrane disruption and intracellular biomass flocculation are primary mechanisms of bacterial killing by real‐time ODT imaging.
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影响因子：
4.6
作者：
Chongsiriwatana NP;Lin JS;Kapoor R;Wetzler M;Rea JAC;Didwania MK;Contag CH;Barron AE
通讯作者：
Barron AE
影响因子：
3.9
作者：
Andreev, Konstantin;Martynowycz, Michael W.;Ivankin, Andrey;Huang, Mia L.;Kuzmenko, Ivan;Meron, Mati;Lin, Binhua;Kirshenbaum, Kent;Gidalevitz, David
通讯作者：
Gidalevitz, David
影响因子：
35
作者：
Kim, Taewoo;Zhou, Renjie;Popescu, Gabriel
通讯作者：
Popescu, Gabriel
影响因子：
13.6
作者：
Bonaventura P;Alcazer V;Mutez V;Tonon L;Martin J;Chuvin N;Michel E;Boulos RE;Estornes Y;Valladeau-Guilemond J;Viari A;Wang Q;Caux C;Depil S
通讯作者：
Depil S
影响因子：
--
作者：
Huang, Wei;Seo, Jiwon;Barron, Annelise E.
通讯作者：
Barron, Annelise E.