Team develops promising new form of antibiotic that makes bacterial cells self-destruct

To address the global threat of antibiotic resistance, scientists are on the hunt for new ways to sneak past a bacterial cell's defense system. Taking what they learned from a previous study on cancer, researchers from the University of Toronto (U of T) have developed novel compounds that trigger bacterial cells to self-destruct.

The new form of antibiotics is designed to target a naturally occurring enzyme – caseinolytic protease proteolytic subunit, ClpP, for short – which chews up old or defective proteins and plays an essential role in cellular housekeeping.

The new compound kicks the ClpP enzyme into overdrive, so it begins chewing up proteins that it is not supposed to, eventually killing its own cell from the inside out.

"Most antibiotics inhibit a process," says Dr. Walid A. Houry, professor of biochemistry at the University of Toronto. "With this approach, we are dysregulating a process, and this allows us to develop this new class of compounds that we eventually hope to get into a clinic." Houry worked closely with Dr. Robert Batey and colleagues to build upon their previous work in this area.

"It turns out that the [enzyme] present in cancer cells is also present in bacteria. For this project, the tricky thing was trying to find a way to hit the bacterial ClpP, but not the human ClpP," Houry adds.

Zdroj obrázku: Lin et al. (2024), Journal of Medicinal Chemistry.