Cresomycin is a synthetic compound developed by a team led by Andrew Myers, Amory Houghton Professor of Chemistry and Chemical Biology at Harvard University. The new molecule demonstrates an improved ability to bind to bacterial ribosomes, which are biomolecular machines that control protein synthesis. Disrupting ribosomal function is a hallmark of many existing antibiotics, but some bacteria have evolved shielding mechanisms that prevent legacy drugs from working. Cresomycin is one of several promising compounds that Myers’ team has developed, with the goal of helping win the war against superbugs.
Bacteria can develop resistance to ribosome-targeting antibiotic drugs by expressing genes that produce enzymes called ribosome-targeting enzymes. These enzymes box out the drug components that are designed to latch onto and disrupt the ribosome, ultimately blocking the drug’s activity. To get around this problem, Myers and team engineered their compound into a rigidified shape that closely resembles its binding target, giving it a stronger grip on the ribosome. The researchers call their drug “pre-organized” for ribosomal binding because it doesn’t need to expend as much energy to bind to the ribosome, making it more difficult for bacteria to develop resistance.