Resistance to β-lactam drugs such as penicillins and cephalosporins has become a worldwide health problem. The World Health Organization has listed multi-drug resistant Acinetobacter baumannii as requiring “top priority for new antibiotic development.” Such antibiotic resistance derives primarily from β-lactamases, including Acinetobacter-derived cephalosporinase (ADC), which bind and destroy antibiotics. A recent study of clinical A. baumannii infections identified the most prevalent ADC β-lactamases conveying antibiotic resistance. This research study seeks to determine the structure and function of two clinical ADC variants: ADC-30 and ADC-162. Using X-ray crystallography and enzyme kinetics, we aim to relate the small changes in structure to their enhanced ability to turn over antibiotics. Characterizing the structure and function of clinical ADC variants will be critical to developing molecules that could inhibit ADCs, thereby restoring antibiotic effectiveness.
Fernando, Micah, "Structural and Functional Characterization of New Clinically Relevant Enzymes Involved in Antibiotic Resistance" (2020). Student Scholars Day Posters. 40.