Old Drugs' Hidden Job

At least two old antibiotics can do some newly discovered tricks, according to a study in Science (2009, 325, 753). Chloramphenicol and tetracycline have been used to combat infection for more than 50 years, and both are thought to work by blocking protein synthesis in bacteria. But the story may be more complicated, report Thomas J. Silhavy of Princeton University, Dominique Belin of the University of Geneva Medical School, Switzerland, and colleagues. They show that chloramphenicol and tetracycline each can precipitate the destruction of the translocation complex, which delivers newly made bacterial proteins to their final destinations. They learned that when a protein cannot thread through the translocation complex, the complex gets jammed. Both antibiotics produce incomplete polypeptides still stuck to ribosomes, which could gum up the complex, triggering its degradation, likely leading to bacterial cell death.