Antibiotic resistant bacteria have emerged in response to the widespread and uncontrolled use of antibiotics. This global public health threat has spurred renewed research efforts into discovering new antibacterial agents, however, this has been insufficient to keep pace with the emergence of new resistant strains. Alternatively, significant efforts have also been devoted to bringing forth small molecules that do not possess inherent antibacterial activity but that enhance the activity of known antibiotics by inhibiting a resistance or virulence mechanism in bacteria. These compounds are known as adjuvants, and their success in the clinic has been borne out for decades by the use of β-lactamase inhibitors in combination with β-lactam antibiotics. However, resistance toward β-lactamase inhibitors has also emerged and threatens their utility. Historically, β-lactams have been the safest and most widely prescribed antibiotics, thus extending the life span of these crucial drugs is of paramount importance. Our research group is interested in developing new small molecules for restoring β-lactam activity against bacteria that have become resistant to them, with a focus on harnessing underexplored mechanisms of inhibition. Our research efforts are divided among two main areas: 1) synthetic and biochemical studies of natural products that restore β-lactam activity against methicillin-resistant <i>Staphylococcus aureus</i> (MRSA), and 2) synthesis and evaluation of inhibitors of β-lactamases expressed by Gram-negative bacteria. Recent results will be presented.

Strategies for restoring β-lactam activity against antibiotic resistant bacteria

256th National Meeting (2018)

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