title: Taking aim at wall teichoic acid synthesis: new biology and new leads for antibiotics.
abstract: Wall teichoic acids are a major and integral component of the Gram-positive cell wall. These structures are present across all species of Gram-positive bacteria and constitute roughly half of the cell wall. Despite decades of careful investigation, a definitive physiological function for wall teichoic acids remains elusive. Advances in the genetics and biochemistry of wall teichoic acid synthesis have led to a new understanding of the complexity of cell wall synthesis in Gram-positive bacteria. Indeed, these innovations have provided new molecular tools available to probe the synthesis and function of these cell wall structures. Among recent discoveries are unexpected roles for wall teichoic acid in cell division, coordination of peptidoglycan synthesis and β-lactam resistance in methicillin-resistant Staphylococcus aureus (MRSA). Notably, wall teichoic acid biogenesis has emerged as a bona fide drug target in S. aureus, where remarkable synthetic-viable interactions among biosynthetic genes have been leveraged for the discovery and characterization of novel inhibitors of the pathway.
authors.affiliation: Michael G DeGroote Institute for Infectious Disease Research and the Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada.
authors.forename: Edward W C
authors.initials: EW
authors.lastname: Sewell
authors.affiliation: Michael G DeGroote Institute for Infectious Disease Research and the Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada.
authors.forename: Eric D
authors.initials: ED
authors.lastname: Brown
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002473:Cell Wall / Q000378:metabolism; D015195:Drug Design; D024881:Drug Resistance, Bacterial; D006094:Gram-Positive Bacteria / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D058990:Molecular Targeted Therapy; D010457:Peptidoglycan / Q000096:biosynthesis; D013211:Staphylococcus aureus / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D013682:Teichoic Acids / Q000096:biosynthesis*
chemical_list: D000900:Anti-Bacterial Agents; D010457:Peptidoglycan; D013682:Teichoic Acids