We are now living in a post-antibiotic era. Bacteria are developing resistance to our current therapeutic arsenal at a rate that far outpaces our ability to create new treatments.  The Review on Antimicrobial Resistance estimates that by 2050 antibiotic resistant infections will kill someone every three seconds. Compounding the problem of antibiotic resistance is the propensity of pathogenic bacteria to form biofilms, which provide a persistent reservoir of infection in patients. Antibiotic treatments alone are inefficient at eradicating or fully preventing bacterial biofilms and can contribute to the enrichment of resistant strains of bacteria.  Compounds that disarm bacterial biofilm formation and resistance mechanisms have potential as novel therapeutics.  In an effort to identify such compounds, we turned to FDA-approved drugs as a rich source of well-studied molecules with known safety and bioavailability profiles.  We hypothesized that this drug repurposing approach would provide us with lead compounds for development and could even identify approved compounds that could rapidly be deployed in the clinic.  To date we have identified four FDA-approved drugs capable of potentiating antibiotics and inhibiting biofilm formation in resistant strains of <i>Staphylococci. </i>From our studies on these drugs, we have extrapolated a putative pharmacophore that has further informed our synthetic efforts and identified a regulatory kinase as our molecular target.  Screening results, biological activity, and mechanism of action studies will be presented.<br/>

Breaking bad bugs with repurposed drugs: Evaluating FDA-approved drugs to target biofilm formation and antibiotic resistance in pathogenic bacteria

2019 Spring National Meeting

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