The looming crisis of antibiotic resistance has galvanized many to explore alternative approaches to antibiotic discovery and development, as traditional strategies have failed to compensate for increasingly resistant bacterial strains. Elemental copper offers an intriguing option in the fight. Widely recognized for its intrinsic bactericidal properties, copper ions are actively mobilized by the innate immune system to counter invading bacteria. Though administration of pure copper is therapeutically intractable, the immune system’s targeted application of copper toxicity can be mimicked and controlled through the use of small molecular ligands. These molecules eschew the “one drug, one target” paradigm of traditional drug discovery, instead often functioning as carriers of copper ions and subverting copper-resistance mechanisms.<br/>            Though this phenomenon of copper-dependent inhibition has been described in the literature for decades, a recent resurgence of interest has propelled the concept from almost accidental identification and characterization to a systematic exploration effort. So far, copper-dependent inhibitors (CDIs) have been identified against a wide array of targets, including Gram-positives, Gram-negatives, mycobacteria, and even pathogenic fungi. Importantly, a surprisingly high number of these CDIs are readily found within existing drug screening libraries, often eclipsing copper-independent inhibitors found in the same subset. Coupled with their amenability to pharmacokinetic optimization and structure-activity relationship studies, CDIs comprise a promising new class of antibiotic compounds.<br/>

Mining for new antimicrobials with copper as the tool

254th National Meeting (2017)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.