Metallo-β-lactamases (MBLs) are Zn(II)-containing enzymes produced by bacteria that inactivate all b-lactam containing antibiotics, including the carbapenems, which are antibiotics of last resort. While the MBLs have been studied for over 50 years, there are no clinical inhibitors for these enzymes. Therefore, there are few antibiotics available to treat bacterial infections caused by bacteria that produce a MBL. To address this problem, a multi-institution team of synthetic organic chemists (UC San Diego), medicinal chemists (UT Austin), microbiologists and MD’s (Case Western and the Cleveland VA), and structural biologists/biochemists (Miami University) teamed together to identify and develop new potential leads. In the seminar, recent results on a new inhibitor scaffold will be presented, along with biophysical studies on several other recently reported compounds in the literature.