An antipsychotic drug used to treat schizophrenia apparently paves the way for developing antibiotics to kill drug-resistant bacteria by knocking out a piece of the bug’s cell wall, researchers in Denmark reported today. The finding could help launch new ways to treat the global health threat of bacteria that have outwitted many, or in some cases all, existing antibiotics.
In the study, which appears today in the journal PLoS ONE, investigators at the University of Southern Denmark examined how thioridazine acted on methicillin-resistant Staphylococcus aureus grown in culture. “When we treat the bacteria with antibiotics alone, nothing happens,” study author Janne Kudsk Klitgaard, PhD, said in a statement. “But when we add thioridazine, something happens. Thioridazine weakens the bacterial cell wall by removing glycine from the cell wall.”
In Staphylococcus bacteria, the amino acid glycine helps form the scaffold of the cell wall. Removing it weakens that scaffold and allows the antibiotic to launch its attack and kill resistant bacteria. Other researchers have found that thioridazine also counteracts drug resistance by disabling efflux pumps that expel antibiotics from the bacterial cell. Researchers in Portugal have shown that thioridazine can successfully treat infection with extensively drug-resistant Mycobacterium tuberculosis when used in combination with antibiotics.
Kudsk Klitgaard and her colleagues will next test thioridazine’s ability to combat drug-resistant bacteria in mice and pigs. The goal is developing drugs for human use that have thioridazine’s mechanisms to kill drug-resistant bacteria but not its adverse effects: the drug can cause a potentially fatal irregular heartbeat.
“We can remove or inactivate parts of thioridazine so we end up with a brand new product,” she said.