Scientists Unveil Innovative Antibiotic Effective Against Resistant Bacteria

An antibiotic developed by researchers at Harvard University and the University of Illinois at Chicago might offer a novel weapon in the fight against drug-resistant bacteria and the diseases they cause. Science reports that pathogenic microorganisms resistant to a range of commonly used antimicrobial drugs are effectively reduced by the antibiotic cresomycin. Long-term cooperation between Yury Polikanov’s lab at UIC, an associate professor of biological sciences, and colleagues at Harvard led to the development of the promising new antibiotic. Harvard researchers help with the design and synthesis of novel medications by drawing on the crucial insights into cellular structure and functions that the UIC scientists provide.

In developing the new antibiotic, the group focused on how many antibiotics interact with a common cellular target – the ribosome – and how drug-resistant bacteria modify their ribosomes to defend themselves.
More than half of all antibiotics inhibit the growth of pathogenic bacteria by interfering with their protein biosynthesis – a complex process catalyzed by the ribosome, which is akin to “a 3D printer that makes all the proteins in a cell,” Polikanov said. Antibiotics bind to bacterial ribosomes and disrupt this protein-manufacturing process, causing bacterial invaders to die.

However, a lot of bacterial species developed basic defenses against this assault. One means of defense for them is to add a single methyl group consisting of one carbon and three hydrogen atoms to their ribosomes, which interferes with the action of antibiotics. Researchers surmised that this defense mechanism was merely bacteria physically obstructing the ribosome-drug binding site, “like putting a push pin on a chair,” according to Polikanov. However, the story the researchers discovered was more nuanced, as they detailed in a paper that was published in Nature Chemical Biology last month. They identified two defensive strategies by viewing drug-resistant ribosomes with nearly atomic precision using a technique known as X-ray crystallography.