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- W2802586146 abstract "New Delhi metallo-β-lactamase-1 (NDM-1) is the major contributor to the emergence of carbapenem resistance in Gram-negative pathogens (GNPs) and has caused many clinically available β-lactam antibiotics to become obsolete. A clinically approved inhibitor of metallo-β-lactamase (MBL) that could restore the activity of carbapenems against resistant GNPs has not yet been found, making NDM-1 a serious threat to human health. Here, we have rationally developed an inhibitor for the NDM-1 enzyme, which has the ability to penetrate the outer membrane of GNPs and inactivate the enzyme by depleting the metal ion (Zn2+) from the active site. The inhibitor reinstated the activity of meropenem against NDM-1 producing clinical isolates of GNPs like Klebsiella pneumoniae and Escherichia coli. Further, the inhibitor efficiently restored meropenem activity against NDM-1 producing K. pneumoniae in a murine sepsis infection model. These findings demonstrate that a combination of the present inhibitor and meropenem has high potential to be translated clinically to combat carbapenem-resistant GNPs." @default.
- W2802586146 created "2018-05-17" @default.
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- W2802586146 date "2018-05-04" @default.
- W2802586146 modified "2023-10-12" @default.
- W2802586146 title "Vancomycin Analogue Restores Meropenem Activity against NDM-1 Gram-Negative Pathogens" @default.
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- W2802586146 doi "https://doi.org/10.1021/acsinfecdis.8b00011" @default.
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- W2802586146 hasPublicationYear "2018" @default.
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