Wall teichoic acids (WTAs) are anionic carbohydrate polymers that are covalently attached to the peptidoglycan layers of many Gram positive organisms, including S. aureus. They comprise 50% of the cell wall mass and have a major influence on cell envelope integrity. They are suggested targets for antibiotics since deleting certain genes in the pathway results in a loss of virulence while deleting others is lethal. We developed a pathway-specific, cell based screen to discover inhibitors of WTA biosynthesis and have identified a potent WTA-active antibiotic. We've also identified a natural product inhibitor of the first step in the biosynthetic pathway.  We will describe studies on the mechanism of action of this compound and on the cellular effects of blocking wall teichoic acid biosynthesis as well as the effects of these compounds on S. aureus cells. Prospects for the use of WTA inhibitors as antibiotics will be discussed.

Cell wall targets for new antibiotics

244th National Meeting (2012)

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