| The beta-lactam antibiotics have been the primary therapeutic treatments to combat common bacterial infections. However, the emergence of beta-lactamase producing multi-drug resistant bacterial pathogens has become a major problem for public health. To address this problem, antibiotics are administered in combination with beta-lactamase inhibitors to treat drug resistance pathogens.;To date, there are only four beta-lactamase inhibitors approved for combination therapy by the US Food and Drug Administration (FDA). With the continuing emergence of drug-resistant beta-lactamase mutants worldwide, there is an urgent need to expand the repertoire of beta-lactamase inhibitors for combination therapy.;The major objective of my research was to identify a new class of beta-lactamase inhibitors that can restore ?-lactam antibiotics activity and use them for combination antibacterial therapy.;I successfully established the use of sulfonyl oxadiazole and 1-hydroxypyridine-2-thiones-6-carboxylic acid as two novel classes of beta-lactamase inhibitors against serine and metallo beta-lactamases respectively that can effectively restore ?-lactam antibiotic activity. Based on a cell-based and biochemical study, I further demonstrated the promising therapeutic potential of these compounds which were subsequently disclosed in two patent applications. |
