Schematic of Wall Teichoic Acid (WTA) biosynthesis in Staphylococcus aureus. Cytoplasmic synthesis begins with the assembly of a disaccharide-phosphate (TarO and A) on which polyribitol- phosphate is polymerized (TarB, F and L) before glycosylation (TarM and S) and ABC transport (TarG and H), followed by transfer to peptidoglycan by putative transferase(s) that remain uncharacterized biochemically. 

The cell envelope of bacteria is comprised of the cytoplasmic membrane, cell wall, outer membrane (in Gram-negative organisms) and cell surface structures.  The cell envelope has a wide variety of important functions including the shape and structural integrity that is provided by the cell wall.  One of the most important functions of the bacterial cell envelope is its role as a permeability barrier.  A lack of basic understanding of the latter has been a major obstacle to the design of new antibiotics.  Researchers in the Brown lab are trying to better understand bacterial permeability and to find ways to perturb this barrier in Gram-negative bacteria.  The Brown research group is also studying wall teichoic acid synthesis in Gram-positive bacteria.  The latter is one of the most enigmatic aspects of bacterial cell wall synthesis and underpins drug resistance in pathogens such a Methicillin Resistant Staphylococcus aureus (MRSA).

 

Selected Publications