Clostridioides difficile (C. difficile) is the leading cause of hospital-acquired diarrhea worldwide, including in Canada. One of the key antibiotics historically used to treat C. difficile infection (CDI) has been metronidazole (MTZ). However, rising treatment failures have led to its removal from standard treatment guidelines in many developed countries, leaving one less viable option for people infected.
In his earlier research, Dr. Abiola Olaitan, Biology Professor at the University of Waterloo, uncovered the molecular mechanism of MTZ resistance, demonstrating that it is modulated by heme, a component found in blood.
In this new study, the Olaitan Lab aimed to identify compounds capable of reversing heme-dependent metronidazole resistance in C. difficile. Through a focused drug screen, the team discovered artemisinin, an antimalarial compound, which restored MTZ susceptibility across a large collection of resistant clinical isolates.
This is the first study to demonstrate that heme-dependent MTZ resistance can be reversed, paving the way for future research into reviving the clinical use of metronidazole against C. difficile.
“We do not have the luxury of moving on to new antibiotics once an existing one fails, because no new antibiotics are being discovered. Therefore, we need to rethink our strategies for addressing resistance by revitalizing existing but previously ineffective antibiotics,” says Dr. Olaitan.
The paper, “Reversion of heme-dependent metronidazole resistance in Clostridioides difficile,” appears in Microbiology Spectrum.