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• W2110778081 abstract "Background. Infections with extended-spectrum β-lactamase–producing Escherichia coli (ESBL-EC) have developed resistance to current therapies. Therefore, the underlying mechanisms of in vivo and in vitro activity of C-terminal–amidated thanatin (A-thanatin) against clinical isolates of ESBL-EC were studied in an attempt to resolve this problem. Methods. A-thanatin was synthesized to determine its minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and kill curve for ESBL-EC. The hemolytic toxicity, stability, and resistance induction of A-thanatin were determined. ESBL-EC–infected mice were used to determine the in vivo activity of A-thanatin. Scanning and transmission electron microscopy and fluorescence microscopy were used to study the underlying mechanism of A-thanatin. Results. A-thanatin is highly effective against ESBL-EC in vitro, with MIC values ≤4 μg/mL. It has been confirmed that A-thanatin has little hemolysis and relative high stability in plasma. Excellent in vivo therapeutic effects were also observed in a septicemic animal model, with survival rates of 50.0%, 66.7%, and 91.7% in the low-dose, middle-dose, and high-dose groups, respectively. Membrane permeabilization may be a major biological action of A-thanatin. Conclusions. Because the development of multidrug resistance limits the available therapeutic options, A-thanatin may provide a novel strategy for treating ESBL-EC infection and other infections due to multidrug-resistant bacteria." @default.
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• W2110778081 date "2011-01-15" @default.
• W2110778081 modified "2023-10-03" @default.
• W2110778081 title "Underlying Mechanism of In vivo and In vitro Activity of C-terminal–amidated Thanatin Against Clinical Isolates of Extended-Spectrum β-lactamase–Producing Escherichia coli" @default.
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• W2110778081 doi "https://doi.org/10.1093/infdis/jiq029" @default.
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