The secret lives of antibiotics are more interesting than we ever knew. Researchers analyzing two commonly prescribed drugs say these medications attack bacteria using never-before-seen techniques—a discovery that could help us develop better drugs in the future. The team published its findings in the Proceedings of the National Academy of Sciences.
Chloramphenicol (CHL) is an aggressive broad-spectrum antibiotic that’s been around since the 1940s. It’s injected intravenously to treat serious infections like meningitis, cholera, plague, and anthrax, but the risks of use are so extreme that it’s typically only used as a drug of last resort.
Linezolid (LZD) is both newer and gentler. It’s prescribed for common illnesses like pneumonia and strep, but has also proven itself against drug-resistant bacteria like the one that causes the staph infection MRSA.
Despite differences in their structure, the two drugs fight disease the same way many other antibiotics do: by sticking to the catalytic center of a bacterial cell and blocking its ability to synthesize proteins. Because other drugs are universal inhibitors—that is, they prevent any and all synthesis—scientists assumed CHL and LZD would be, too.
Researchers at the University of Illinois, Chicago were not content to assume. They wanted to know for sure what the two antibiotics were up to. They cultured colonies of E. coli bacteria, exposed them to strong doses of CHL and LZD, then sequenced the beleaguered bacteria’s genes to see what was going on inside.
As expected, CHL and LZD were all up on the bacteria’s ribosomes, frustrating its attempts to put proteins together. But the drugs weren’t as totalitarian as scientists had believed. Instead, their approach seemed both specific and context-dependent, switching targets based on which amino acids were present.
"These findings indicate that the nascent protein modulates the properties of the ribosomal catalytic center and affects binding of its ligands, including antibiotics," co-author Nora Vazquez-Laslop said in a statement. In other words: It seems amino acids have a lot more influence than we realized.
As so often happens in science, finding these answers also raised a lot of questions (like "How many other antibiotics have we mischaracterized?"), but it also opens a door for medical science, said co-author Alexander Mankin.
"If you know how these inhibitors work, you can make better drugs and make them better tools for research. You can also use them more efficiently to treat human and animal diseases."