2014 S3: Allison VanDine, MS3

Characterizing an inhibitory compound to combat antibiotic resistance in Acinetobacter

A strain of pathogenic bacteria, Acinetobacter baumannii, is developing resistance at an alarming rate to β-lactam antibiotics. Much of this resistance is attributed to the expression of class C β-lactamases, termed Acinetobacter-derived Cephalosporinases (ADCs). One of these β-lactamases, ADC-7, can deactivate the β-lactam ring present in a broad spectrum of existing antibiotics. A novel class of inhibitors, boronic acid transition state inhibitors (BATSIs), has been synthesized to combat this resistance mechanism. In this study, an inhibitor (CR157) was characterized for its ability to bind and inhibit ADC-7. CR157 was discovered to bind ADC-7 with high affinity and inhibit its ability to deactivate a common antibiotic. Additionally, the X-ray crystal structure of the ADC-7/CR157 complex was determined at 2.03 Å. The ADC-7/CR157 complex provides insight to the inhibitory capabilities of CR157, as well as contributing to the structure-based optimization of future β-lactamase inhibitors.

Faculty Mentor: Brad Wallar, Chemistry

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