Nitric Oxide Battles Tuberculosis

A promising class of experimental bicyclic nitroimidazole drugs kills tuberculosis bacteria by unleashing lethal nitric oxide inside the cells, according to a report in Science (2008, 322, 1392). Release of the highly reactive NO is "akin to a bomb blast that kills the bacteria from within," says Clifton E. Barry III of the National Institute of Allergy & Infectious Diseases, in Bethesda, Md. Barry and his colleagues found that an enzyme in the tuberculosis bacterium metabolizes drug candidates such as PA-824, in the process releasing nitrous acid, which in turn forms NO. PA-824 and a second bicyclic nitroimidazole known as OPC-67683 are now in human clinical trials. The compounds are attractive because they kill both replicating and nonreplicating tuberculosis bacteria. Researchers suspect that conventional treatment for the disease takes at least six months because it largely fails to kill nonreplicating bacteria.