Combinatorial antimicrobial efficacy and mechanism of linalool against clinically relevant klebsiella pneumoniae

Yang, Shun-Kai and Yusoff, Khatijah and Ajat, Mokrish and Wee, Chien-Yeong and Yap, Polly-Soo-Xi and Lim, Swee-Hua-Erin and Lai, Kok-Song (2021) Combinatorial antimicrobial efficacy and mechanism of linalool against clinically relevant klebsiella pneumoniae. Frontiers in Microbiology, 12. ISSN 1664-302X, DOI

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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 mu g/ml) and in combination with meropenem (5,625 mu g/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.

Item Type: Article
Funders: University Putra Malaysia Graduate Research Fund, Higher Colleges of Technology Interdisciplinary Research Grant (1319)
Uncontrolled Keywords: Adjuvant; Antibiotic combinatory therapy; Carbapenemase-producing Klebsiella pneumoniae; Linalool; Membrane disruption; Oxidative stress
Subjects: Q Science > QR Microbiology
Divisions: Faculty of Medicine
Depositing User: Ms Zaharah Ramly
Date Deposited: 14 Mar 2022 03:22
Last Modified: 14 Mar 2022 03:22

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