A revised pathway proposed for Staphylococcus aureus wall teichoic acid biosynthesis based on in vitro reconstitution of the intracellular steps.
Resistance to every family of clinically used antibiotics has emerged, and there is a pressing need to explore unique antibacterial targets. Wall teichoic acids (WTAs) are anionic polymers that coat the cell walls of many Gram-positive bacteria. Because WTAs play an essential role in Staphylococcus aureus colonization and infection, the enzymes involved in WTA biosynthesis are proposed to be targets for antibiotic development. To facilitate the discovery of WTA inhibitors, we have reconstituted the intracellular steps of S. aureus WTA biosynthesis. We show that two intracellular steps in the biosynthetic pathway are different from what was proposed. The work reported here lays the foundation for the discovery and characterization of inhibitors of WTA biosynthetic enzymes to assess their potential for treating bacterial infections.
Brown
Stephanie
S
Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.
Zhang
Yu-Hui
YH
Walker
Suzanne
S
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002240:Carbohydrate Sequence; D002473:Cell Wall / Q000187:drug effects* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004586:Electrophoresis; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000473:pathology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D013682:Teichoic Acids / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000737:chemistry; D013997:Time Factors
D000900:Anti-Bacterial Agents; D013682:Teichoic Acids