Antibiotic resistance is a growing threat, partially due to expression of β-lactamase enzymes by bacteria. These enzymes hydrolyze antibacterial drugs in the β-lactam class to make them inactive. This work aims to take advantage of this resistance by utilizing β-lactamase-activated prodrugs of an antimicrobial chelator. We report progress toward the development of these prochelators as agents to selectively kill resistant strains of bacteria by interfering with cellular homeostasis of essential metals including copper. Results presented include the design, synthesis, measurement of enzyme-mediated chelator release, and antibacterial activity of prochelators. These results demonstrate that the antibacterial prochelator strategy is a promising method for treatment of drug-resistant bacterial infections by manipulating metals at the host-pathogen interface.

Targeting drug-resistant bacteria with enzyme-activated prochelators

254th National Meeting (2017)

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