MIT and Boston University researchers have discovered that the drug hydroxyurea kills bacteria by inducing them to produce molecules toxic to themselves – a conclusion that raises the possibility of finding new antibiotics that use similar mechanisms.
Hydroxyurea inhibits the enzyme critical for making the building blocks for DNA, so for decades it has been used to study the consequences of inhibiting DNA replication in E. coli, yeast and mammalian cells. It is also sometimes used in chemotherapy to halt the growth of cancer cells.
The research team, led by biologist Graham Walker of MIT and bioengineer James Collins of Boston University, showed that cells don’t die after hydroxyurea treatment because their DNA replication is blocked, but because the blockage sets in motion a chain of cellular events that culminates in the production of hydroxyl radicals. Those radicals are highly reactive and can damage cellular molecules such as nucleic acids, lipids and proteins.