Methicilin-resistant <i>Staphylococcus aureus</i> (MRSA) is a gram-positive bacteria that can cause multiple infections including surgical site and bloodstream infections. Many MRSA strains are resistant to several classes of antibiotics, making them very difficult to treat. Surgical-site infections can lead to the formation of biofilms, bacteria that congregate on a surface enveloped in an extracellular matrix. Biofilm based infections are responsible for up to 80% of chronic infections and are up to 1000 times more tolerant of antibiotic treatment than planktonic bacteria. Since 2013, MRSA bloodstream infections have not significantly decreased as expected, signaling the need for new therapies to treat these infections. The first of two novel approaches in combating MRSA includes antibiotic adjuvants which are compounds that enhance the activity of antibiotics and suppress resistance development in bacteria. The second approach is through biofilm inhibition, where compounds can impede the formation and promote the disassembly of biofilms. We have identified a small molecule scaffold that potentiates antibiotics and inhibits biofilm formation in MRSA. In an effort to understand the basis for this activity, we screened a small library of compounds to establish an initial structure-activity relationship (SAR) and inform the design and synthesis of derivatives. SAR, synthetic approaches, and biological assay results will be presented.

Identification and structure-activity relationship of a small molecule scaffold with novel antibiotic adjuvant and biofilm inhibition properties in methicillin-resistant <i>Staphylococcus aureus </i>(MRSA)

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

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Identification and structure-activity relationship of a small molecule scaffold with novel antibiotic adjuvant and biofilm inhibition properties in methicillin-resistant Staphylococcus aureus (MRSA)