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Combinatorial Antimicrobial Efficacy and Mechanism of Linalool Against Clinically Relevant Klebsiella pneumoniae

Antibiotic–adjuvant combinatory therapy serves as a viable treatment option in addressing antibiotic resistance in the clinical setting. This study was carried out to assess and characterize the adjuvant potential and mode of action of linalool against carbapenemase-producing Klebsiella pneumoniae (...

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Autores principales: Yang, Shun-Kai, Yusoff, Khatijah, Ajat, Mokrish, Wee, Chien-Yeong, Yap, Polly-Soo-Xi, Lim, Swee-Hua-Erin, Lai, Kok-Song
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010000/
https://www.ncbi.nlm.nih.gov/pubmed/33815320
http://dx.doi.org/10.3389/fmicb.2021.635016
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author Yang, Shun-Kai
Yusoff, Khatijah
Ajat, Mokrish
Wee, Chien-Yeong
Yap, Polly-Soo-Xi
Lim, Swee-Hua-Erin
Lai, Kok-Song
author_facet Yang, Shun-Kai
Yusoff, Khatijah
Ajat, Mokrish
Wee, Chien-Yeong
Yap, Polly-Soo-Xi
Lim, Swee-Hua-Erin
Lai, Kok-Song
author_sort Yang, Shun-Kai
collection PubMed
description Antibiotic–adjuvant combinatory therapy serves as a viable treatment option in addressing antibiotic resistance in the clinical setting. This study was carried out to assess and characterize the adjuvant potential and mode of action of linalool against carbapenemase-producing Klebsiella pneumoniae (KPC-KP). Linalool exhibited bactericidal activity alone (11,250 μg/ml) and in combination with meropenem (5,625 μg/ml). Comparative proteomic analysis showed significant reduction in the number of cytoplasmic and membrane proteins, indicating membrane damage in linalool-treated KPC-KP cells. Upregulation of oxidative stress regulator proteins and downregulation of oxidative stress-sensitive proteins indicated oxidative stress. Zeta potential measurement and outer membrane permeability assay revealed that linalool increases the bacterial surface charge as well as the membrane permeability. Intracellular leakage of nucleic acid and proteins was detected upon linalool treatment. Scanning and transmission electron microscopies further revealed the breakage of bacterial membrane and loss of intracellular materials. Linalool induced oxidative stress by generating reactive oxygen species (ROS) which initiates lipid peroxidation, leading to damage of the bacterial membrane. This leads to intracellular leakage, eventually killing the KPC-KP cells. Our study demonstrated that linalool possesses great potential in future clinical applications as an adjuvant along with existing antibiotics attributed to their ability in disrupting the bacterial membrane by inducing oxidative stress. This facilitates the uptake of antibiotics into the bacterial cells, enhancing bacterial killing.
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spelling pubmed-80100002021-04-01 Combinatorial Antimicrobial Efficacy and Mechanism of Linalool Against Clinically Relevant Klebsiella pneumoniae Yang, Shun-Kai Yusoff, Khatijah Ajat, Mokrish Wee, Chien-Yeong Yap, Polly-Soo-Xi Lim, Swee-Hua-Erin Lai, Kok-Song Front Microbiol Microbiology Antibiotic–adjuvant combinatory therapy serves as a viable treatment option in addressing antibiotic resistance in the clinical setting. This study was carried out to assess and characterize the adjuvant potential and mode of action of linalool against carbapenemase-producing Klebsiella pneumoniae (KPC-KP). Linalool exhibited bactericidal activity alone (11,250 μg/ml) and in combination with meropenem (5,625 μg/ml). Comparative proteomic analysis showed significant reduction in the number of cytoplasmic and membrane proteins, indicating membrane damage in linalool-treated KPC-KP cells. Upregulation of oxidative stress regulator proteins and downregulation of oxidative stress-sensitive proteins indicated oxidative stress. Zeta potential measurement and outer membrane permeability assay revealed that linalool increases the bacterial surface charge as well as the membrane permeability. Intracellular leakage of nucleic acid and proteins was detected upon linalool treatment. Scanning and transmission electron microscopies further revealed the breakage of bacterial membrane and loss of intracellular materials. Linalool induced oxidative stress by generating reactive oxygen species (ROS) which initiates lipid peroxidation, leading to damage of the bacterial membrane. This leads to intracellular leakage, eventually killing the KPC-KP cells. Our study demonstrated that linalool possesses great potential in future clinical applications as an adjuvant along with existing antibiotics attributed to their ability in disrupting the bacterial membrane by inducing oxidative stress. This facilitates the uptake of antibiotics into the bacterial cells, enhancing bacterial killing. Frontiers Media S.A. 2021-03-17 /pmc/articles/PMC8010000/ /pubmed/33815320 http://dx.doi.org/10.3389/fmicb.2021.635016 Text en Copyright © 2021 Yang, Yusoff, Ajat, Wee, Yap, Lim and Lai. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Yang, Shun-Kai
Yusoff, Khatijah
Ajat, Mokrish
Wee, Chien-Yeong
Yap, Polly-Soo-Xi
Lim, Swee-Hua-Erin
Lai, Kok-Song
Combinatorial Antimicrobial Efficacy and Mechanism of Linalool Against Clinically Relevant Klebsiella pneumoniae
title Combinatorial Antimicrobial Efficacy and Mechanism of Linalool Against Clinically Relevant Klebsiella pneumoniae
title_full Combinatorial Antimicrobial Efficacy and Mechanism of Linalool Against Clinically Relevant Klebsiella pneumoniae
title_fullStr Combinatorial Antimicrobial Efficacy and Mechanism of Linalool Against Clinically Relevant Klebsiella pneumoniae
title_full_unstemmed Combinatorial Antimicrobial Efficacy and Mechanism of Linalool Against Clinically Relevant Klebsiella pneumoniae
title_short Combinatorial Antimicrobial Efficacy and Mechanism of Linalool Against Clinically Relevant Klebsiella pneumoniae
title_sort combinatorial antimicrobial efficacy and mechanism of linalool against clinically relevant klebsiella pneumoniae
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010000/
https://www.ncbi.nlm.nih.gov/pubmed/33815320
http://dx.doi.org/10.3389/fmicb.2021.635016
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