Heat shock potentiates aminoglycosides against gram-negative bacteria by enhancing antibiotic uptake, protein aggregation, and ROS.
Heat shock potentiates aminoglycosides against gram-negative bacteria by enhancing antibiotic uptake, protein aggregation, and ROS.
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热休克通过增强抗生素摄取、蛋白质聚集和ROS增强氨基糖苷类抗生素对革兰氏阴性菌的抵抗力。
DOI：
10.1073/pnas.2217254120
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发表时间：
2023-03-21
影响因子：
11.1
通讯作者：
Fu, Xinmiao
中科院分区：
文献类型：
--
作者：
Lv, Boyan;Huang, Xuebing;Lijia, Chenchen;Ma, Yuelong;Bian, Mengmeng;Li, Zhongyan;Duan, Juan;Zhou, Fang;Yang, Bin;Qie, Xingwang;Song, Yizhi;Wood, Thomas K.;Fu, Xinmiao
关键词：
Bacterial antibiotic resistance has become a severe threat to human and animal health. Increasing the efficacy of existing antibiotics is a promising strategy against antibiotic resistance. Here, we report that thermal treatment dramatically enhances the efficacy of aminoglycoside antibiotics in killing various bacteria, including multidrug-resistant pathogens. Mechanistically, such potentiation effect of thermal treatment is achieved by promoting the bacterial uptake of and enhancing the downstream lethality of aminoglycosides. Our study demonstrates a high potential of thermal treatment in curing antibiotic-resistance–associated bacterial infections when combined with aminoglycosides, thus expanding on its current application in treating tumors. The potentiation of antibiotics is a promising strategy for combatting antibiotic-resistant/tolerant bacteria. Herein, we report that a 5-min sublethal heat shock enhances the bactericidal actions of aminoglycoside antibiotics by six orders of magnitude against both exponential- and stationary-phase Escherichia coli. This combined treatment also effectively kills various E. coli persisters, E. coli clinical isolates, and numerous gram-negative but not gram-positive bacteria and enables aminoglycosides at 5% of minimum inhibitory concentrations to eradicate multidrug-resistant pathogens Acinetobacter baumannii and Klebsiella pneumoniae. Mechanistically, the potentiation is achieved comprehensively by heat shock-enhanced proton motive force that thus promotes the bacterial uptake of aminoglycosides, as well as by increasing irreversible protein aggregation and reactive oxygen species that further augment the downstream lethality of aminoglycosides. Consistently, protonophores, chemical chaperones, antioxidants, and anaerobic culturing abolish heat shock-enhanced aminoglycoside lethality. We also demonstrate as a proof of concept that infrared irradiation- or photothermal nanosphere-induced thermal treatments potentiate aminoglycoside killing of Pseudomonas aeruginosa in a mouse acute skin wound model. Our study advances the understanding of the mechanism of actions of aminoglycosides and demonstrates a high potential for thermal ablation in curing bacterial infections when combined with aminoglycosides.
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影响因子：
5.2
作者：
Gao Y;Chen Z;Yao W;Li D;Fu X
通讯作者：
Fu X
DOI：
10.1073/pnas.83.16.6164
发表时间：
1986-08-01
影响因子：
11.1
作者：
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通讯作者：
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作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
Dwyer, Daniel J.;Kohanski, Michael A.;Collins, James J.
通讯作者：
Collins, James J.