Staphylococcus aureus is a gram-positive pathogen that causes systemic and soft tissue infections in humans and livestock. S. aureus forms robust biofilms that are recalcitrant to clearance by antibiotics and readily develops resistance to many common antibiotics. We are interested in investigating novel drug targets in S. aureus that could be exploited to simultaneously target antibiotic resistance and biofilm formation. The PASTA kinase Stk1 has been identified as a master regulator of genes involved in both biofilm formation and resistance to β-lactams and vancomycin. We have identified a library of related compounds that inhibit the kinase domain of Stk1, leading to inhibition of biofilm formation and potentiation of β-lactam and vancomycin in resistant strains. Initial screenings of a focused compound library provided a preliminary structure-activity relationship (SAR) that informed our synthesis of derivatives to expand the SAR and create more potent derivatives. Biological data, SAR, and synthetic details will be presented.

Synthesis and evaluation of small molecules that inhibit Stk1, a Ser/Thr kinase that controls antibiotic resistance and virulence gene regulation in Staphylococcus aureus

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.