Probing Teichoic Acid Genetics with Bioactive Molecules Reveals New Interactions among Diverse Processes in Bacterial Cell Wall Biogenesis

The bacterial cell wall has been a celebrated target for antibiotics and holds real promise for the discovery of new antibacterial chemical matter. In addition to peptidoglycan, the walls of Gram-positive bacteria contain large amounts of the polymer teichoic acid, covalently attached to peptidoglycan. Recently, wall teichoic acid was shown to be essential to the proper morphology of Bacillus subtilis and an important virulence factor for Staphylococcus aureus. Additionally, recent studies have shown that the dispensability of genes encoding teichoic acid biosynthetic enzymes is paradoxical and complex. Here, we report on the discovery of a promoter (P(ywaC)), which is sensitive to lesions in teichoic acid synthesis. Exploiting this promoter through a chemical-genetic approach, we revealed surprising interactions among undecaprenol, peptidoglycan, and teichoic acid biosynthesis that help explain the complexity of teichoic acid gene dispensability. Furthermore, the new reporter assay represents an exciting avenue for the discovery of antibacterial molecules.