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光控选择性细菌细胞膜相互作用的门控和增强抗菌活性促进伤口愈合。

Photo-Controlled Gating of Selective Bacterial Membrane Interaction and Enhanced Antibacterial Activity for Wound Healing.

机构信息

Department of Organic Chemistry, Indian Institute of Science, Bengaluru, 560012, India.

Department of Biochemistry, Indian Institute of Science, Bengaluru, 560012, India.

出版信息

Angew Chem Int Ed Engl. 2024 Jan 2;63(1):e202314804. doi: 10.1002/anie.202314804. Epub 2023 Nov 29.

Abstract

Reversible biointerfaces are essential for on-demand molecular recognition to regulate stimuli-responsive bioactivity such as specific interactions with cell membranes. The reversibility on a single platform allows the smart material to kill pathogens or attach/detach cells. Herein, we introduce a 2D-MoS functionalized with cationic azobenzene that interacts selectively with either Gram-positive or Gram-negative bacteria in a light-gated fashion. The trans conformation (trans-Azo-MoS ) selectively kills Gram-negative bacteria, whereas the cis form (cis-Azo-MoS ), under UV light, exhibits antibacterial activity against Gram-positive strains. The mechanistic investigation indicates that the cis-Azo-MoS exhibits higher affinity towards the membrane of Gram-positive bacteria compared to trans-Azo-MoS . In case of Gram-negative bacteria, trans-Azo-MoS internalizes more efficiently than cis-Azo-MoS and generates intracellular ROS to kill the bacteria. While the trans-Azo-MoS exhibits strong electrostatic interactions and internalizes faster into Gram-negative bacterial cells, cis-Azo-MoS primarily interacts with Gram-positive bacteria through hydrophobic and H-bonding interactions. The difference in molecular mechanism leads to photo-controlled Gram-selectivity and enhanced antibacterial activity. We found strain-specific and high bactericidal activity (minimal bactericidal concentration, 0.65 μg/ml) with low cytotoxicity, which we extended to wound healing applications. This methodology provides a single platform for efficiently switching between conformers to reversibly control the strain-selective bactericidal activity regulated by light.

摘要

可还原生物界面对于按需分子识别至关重要,可用于调节刺激响应生物活性,例如与细胞膜的特异性相互作用。在单个平台上的可逆性允许智能材料杀死病原体或附着/脱离细胞。在此,我们介绍了一种二维二硫化钼,其功能化有阳离子型偶氮苯,可通过光门方式选择性地与革兰氏阳性菌或革兰氏阴性菌相互作用。反式构象(trans-Azo-MoS )选择性地杀死革兰氏阴性菌,而顺式构象(cis-Azo-MoS )在紫外光下对革兰氏阳性菌株表现出抗菌活性。机理研究表明,与 trans-Azo-MoS 相比,cis-Azo-MoS 对革兰氏阳性菌的膜具有更高的亲和力。对于革兰氏阴性菌,trans-Azo-MoS 比 cis-Azo-MoS 更有效地内化,并产生细胞内 ROS 来杀死细菌。虽然 trans-Azo-MoS 表现出强静电相互作用并更快地内化到革兰氏阴性细菌细胞中,但 cis-Azo-MoS 主要通过疏水和氢键相互作用与革兰氏阳性细菌相互作用。分子机制的差异导致光控革兰氏选择性和增强的抗菌活性。我们发现具有菌株特异性和高杀菌活性(最小杀菌浓度,0.65 μg/ml)且细胞毒性低的方法,我们将其扩展到伤口愈合应用中。该方法提供了一个单一平台,可在构象之间高效切换,以可逆地控制由光调节的菌株选择性杀菌活性。

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