Bacterial cell-wall synthesis probed

Teichoic acids found in the cell walls of gram-positive bacteria have been shown to be essential for survival or virulence (host infectivity) of the bacteria. But no antibiotics have been directed against TagA and TagB, the enzymes that had been predicted to catalyze biosynthesis of the acids, in part because the enzymes' role has been uncertain. Suzanne Walker and her coworkers at Harvard Medical School have now synthesized the first modified substrates (one shown) of TagA and TagB, which do appear to catalyze the initial steps in teichoic acid biosynthesis, and they are using the substrates to study key steps in the biosynthesis (ACS Chem. Biol., published online Jan. 24, dx.doi.org/10.1021/cb0500041). The work helps verify that TagA and TagB play an essential role as survival or virulence factors, and it "lays the foundation for detailed mechanistic and structural studies," Walker and coworkers note. In addition, the work should facilitate consideration of TagA and TagB as potential targets for a new type of antibiotic.