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Suppression of β-Lactam Resistance by Aspergillomarasmine A is Influenced by Both the Metallo-β-Lactamase Target and the Antibiotic Partner

Antimicrob Agents Chemother. 2020; 
Rotondo CM,,, Sychantha D,,, Koteva K,,, Wright GD,,.
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摘要

The rise of Gram-negative pathogens expressing metallo-β-lactamases (MBLs) is a growing concern, threatening the efficacy of β-lactam antibiotics, in particular, the carbapenems. There are no inhibitors of MBLs in current clinical use. Aspergillomarasmine A (AMA) is an MBL inhibitor isolated from Aspergillus versicolor with both in vitro and in vivo ability to rescue meropenem activity in MBL-producing bacteria. Here we systematically explored the pairing of AMA with six β-lactam antibiotic partners against nineteen MBLs from each subclass (B1, B2, B3). Cell-based assays with Escherichia coli and Klebsiella pneumoniae showed that bacteria producing NDM-1 and VIM-2 of subclass B1 were the most susceptible to ... More

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