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

Abstract

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 the ability to rescue meropenem activity in MBL-producing bacteria both in vitro and in vivo . Here, we systematically explored the pairing of AMA with six β-lactam antibiotic partners against 19 MBLs from three subclasses (B1, B2, and B3).