Staphylococcus aureus is a gram-positive bacterium responsible for numerous infections including those of the skin, heart, and soft tissue.  It is one of the leading causes of hospital-acquired infections and in extreme cases can lead to death.  Due to its continued development of resistance to current antibiotics there is an urgent need for new drugs to battle this pathogenic bacteria.    The purpose of this research is to develop new therapeutic agents that inhibit the biosynthesis of staphyloferrin A (SfnA), an iron-binding siderophore produced by S. aureus. This research characterizes and carries out mechanistic inhibition studies of the ornithine racemase, SfnaC, located in the staphyloferrin A biosynthetic pathway. Results of characterization studies include cloning, overexpression and purification of recombinant SfnaC, results of in vitro activity assays, UV-vis spectral characterization of bound pyridoxal  5'-phosphate (PLP), and initiation of the synthesis of two mechanistic-based inhibitors, an ornithine phosphonate and a fluoroornithine analogue.

Characterization and inhibition studies of the ornithine racemase involved in staphyloferrin A biosynthesis in Staphylococcus aureus

245th National Meeting (2013)

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