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- W4281780633 abstract "Gram-negative bacteria, especially the ones with multidrug resistance, post dire challenges to antibiotic treatments due to the presence of the outer membrane (OM), which blocks the entry of many antibiotics. Current solutions for such permeability issues, namely lipophilic-cationic derivatization of antibiotics and sensitization with membrane-active agents, cannot effectively potentiate the large, globular, and hydrophilic antibiotics such as vancomycin, due to ineffective disruption of the OM. Here, we present our solution for high-degree OM binding of vancomycin via a hybrid derivatization-for-sensitization approach, which features a combination of LPS-targeting lipo-cationic modifications on vancomycin and OM disruption activity from a sensitizing adjuvant. 106- to 107-fold potentiation of vancomycin and 20-fold increase of the sensitizer's effectiveness were achieved with a combination of a vancomycin derivative and its sensitizer. Such potentiation is the result of direct membrane lysis through cooperative membrane binding for the sensitizer-antibiotic complex, which strongly promotes the uptake of vancomycin and adds to the extensive antiresistance effectiveness. The potential of such derivatization-for-sensitization approach was also supported by the combination's potent in vivo antimicrobial efficacy in mouse model studies, and the expanded application of such strategy on other antibiotics and sensitizer structures." @default.
- W4281780633 created "2022-06-13" @default.
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- W4281780633 date "2022-06-03" @default.
- W4281780633 modified "2023-10-16" @default.
- W4281780633 title "Potentiation of Vancomycin: Creating Cooperative Membrane Lysis through a “Derivatization-for-Sensitization” Approach" @default.
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- W4281780633 doi "https://doi.org/10.1021/jacs.2c03784" @default.
- W4281780633 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35657057" @default.
- W4281780633 hasPublicationYear "2022" @default.
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