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• W3101589056 abstract "Hydroxychavicol (HC), found abundantly in Piper betle leaves is credited with antimicrobial property . Previously we had shown HC induces reactive oxygen species mediated DNA damage in bacterial cells. HC also resulted in membrane compromise revealing its pleiotropic effects on cellular targets. The kinetics and exact sequence of events leading to inhibition of growth and cell death in E. coli after HC treatment remains poorly understood. We show that sub-lethal concentration (125 μg/mL) of HC causes cellular filamentation within 1 h of treatment, while a higher concentration (750 μg/mL) induces cell breakage. HC-treated cells were found to experience oxidative stress as early as 10 min, while evidence of membrane damage was apparent at 30 min. DNA damage repair genes were found to be activated at 60 min. Interestingly, HC-induced cell permeabilization was inhibited and enhanced by external Mg 2+ and EDTA, respectively, suggesting that HC damages the outer membrane . Kinetic experiments revealed that HC-treated cells underwent oxidative stress, membrane damage and DNA damage in that order. Because gram negative bacteria such as E. coli are refractory to several antibiotics due to the presence of the outer membrane, we hypothesized that HC pretreatment would sensitize E. coli to hydrophobic antibiotics. Our study reveals for the first time that HC could sensitize bacteria to clinically used antibiotics due to its outer membrane damaging property. • Hydroxychavicol causes membrane damage in E. coli by stripping magnesium ions. • The kinetics of the damage to various targets was elucidated. • Hydroxychavicol induces oxidative stress followed by membrane and DNA damage. • Hydroxychavicol sensitizes E. coli to clinically used antibiotics." @default.
• W3101589056 created "2020-11-23" @default.
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• W3101589056 date "2021-01-01" @default.
• W3101589056 modified "2023-09-27" @default.
• W3101589056 title "Membrane damage precedes DNA damage in hydroxychavicol treated E. coli cells and facilitates cooperativity with hydrophobic antibiotics" @default.
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• W3101589056 doi "https://doi.org/10.1016/j.biochi.2020.11.008" @default.
• W3101589056 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/33181225" @default.
• W3101589056 hasPublicationYear "2021" @default.
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