Theaflavin-3,3´-digallate increases the antibacterial activity of β-lactam antibiotics by inhibiting metallo-β-lactamase activity.

ABSTRACT: Metallo-β-lactamases (MBLs) are some of the best known β-lactamases produced by common Gram-positive and Gram-negative pathogens and are crucial factors in the rise of bacterial resistance against β-lactam antibiotics. Although many types of β-lactamase inhibitors have been successfully developed and used in clinical settings, no MBL inhibitors have been identified to date. Nitrocefin, checkerboard and time-kill assays were used to examine the enzyme behaviour in vitro. Molecular docking calculation, molecular dynamics simulation, calculation of the binding free energy and ligand-residue interaction decomposition were used for mechanistic research. The behaviour of the enzymes in vivo was investigated by a mouse infection experiment. We showed that theaflavin-3,3´-digallate (TFDG), a natur

SUBMITTER: Teng Z 

PROVIDER: S-EPMC6787515 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature