Antimicrobial activity and mode of action of terpene linalyl anthranilate against carbapenemase-producing Klebsiella pneumoniae

查看全文 作　　者：Shun-Kai [1]Yang;Khatijah [2]Yusoff;Mokrish [3]Ajat;Wai-Sum [4]Yap;Swee-Hua Erin [5]Lim;Kok-Song [5]Lai

机构地区：[1]Department of Cell and Molecular Biology,Faculty of Biotechnology and Biomolecular Sciences,Universiti Putra Malaysia,43400,Serdang,Selangor,Malaysia;[2]Department of Microbiology,Faculty of Biotechnology and Biomolecular Sciences,Universiti Putra Malaysia,43400,Serdang,Selangor,Malaysia;[3]Department of Veterinary Preclinical Sciences,Faculty of Veterinary Medicine,Universiti Putra Malaysia,43400,Serdang,Selangor,Malaysia;[4]Department of Biotechnology,Faculty of Applied Sciences,UCSI University,56000,Cheras,Kuala Lumpur,Malaysia;[5]Health Sciences Division,Abu Dhabi Women’s College,Higher Colleges of Technology,41012,Abu Dhabi,United Arab Emirates

出　　处：《Journal of Pharmaceutical Analysis》索引2021年第11卷第2期,共10页

基　　金：supported by the Higher College of Technology (HCT) Interdisciplinary Research Grant (Grant No. 113118);the Malaysian Medical Association Grant, and the UCSI PSIF Grant (Grant No. Proj-2019-In-Fas-062)。 摘　　要：Mining of plant-derived antimicrobials is the major focus at current to counter antibiotic resistance. This study was conducted to characterize the antimicrobial activity and mode of action of linalyl anthranilate(LNA) against carbapenemase-producing Klebsiella pneumoniae(KPC-KP). LNA alone exhibited bactericidal activity at 2.5%(V/V), and in combination with meropenem(MPM) at 1.25%(V/V). Comparative proteomic analysis showed a significant reduction in the number of cytoplasmic and membrane proteins,indicating membrane damage in LNA-treated KPC-KP cells. Up-regulation of oxidative stress regulator proteins and down-regulation of oxidative stress-sensitive proteins indicated oxidative stress. Zeta potential measurement and outer membrane permeability assay revealed that LNA increases both bacterial surface charge and membrane permeability. Ethidium bromide influx/efflux assay showed increased uptake of ethidium bromide in LNA-treated cells, inferring membrane damage. Furthermore, intracellular leakage of nucleic acid and proteins was detected upon LNA treatment. Scanning and transmission electron microscopies again revealed the breakage of bacterial membrane and loss of intracellular materials. LNA was found to induce oxidative stress by generating reactive oxygen species(ROS) that initiate lipid peroxidation and damage the bacterial membrane. In conclusion, LNA generates ROS, initiates lipid peroxidation, and damages the bacterial membrane, resulting in intracellular leakage and eventually killing the KPC-KP cells. 关键词：Comparative proteomic KPC-KP Linalyl anthranilate Membrane damage ROS

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Antimicrobial activity and mode of action of terpene linalyl anthranilate against carbapenemase-producing Klebsiella pneumoniae

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