Native State Mass Spec Used to Evaluate How Metallo-Beta -Lactamase Inhibitors Work

Researchers from the Miami University in Ohio say they have found better way to evaluate how potential inhibitors work on antibiotic-resistant bacteria. Using native state mass spectrometry, they say, allows scientists to quickly identify the best candidates for effective clinical drugs, particularly in cases where bacteria can no longer be treated with antibiotics alone.

Before any new inhibitor can be used in the clinic, scientists need to have a complete understanding of how the inhibitor works. In the current study, Caitlyn Thomas, a Ph.D. candidate in chemistry, who will present the study today at the American Society for Microbiology World Microbe Forum, and her colleagues studied a bacterial protein called metallo-beta-lactamase, which renders many clinical strains of bacteria resistant to all penicillin-like antibiotics.

While many research labs are attempting to create new inhibitors that inactivate metallo-beta-lactamases, Thomas and collaborators instead analyzed how these new inhibitors work. "Because metallo-beta-lactamases contain two metal ions we are able to use a variety of spectroscopic techniques to study them," said Thomas. "These experiments give us more insight into how to inhibitor behaves and whether it could potentially be a candidate for clinical use in the future."

Hundreds of potential inhibitors have been reported in the literature, and several patents have been filed dealing with metallo-beta-lactamase inhibitors. Some of the reported inhibitors work by removing a required component of the metallo-beta-lactamase. These same inhibitors may remove this same required component of other proteins in humans, causing serious side effects. Other inhibitors bind directly to the metallo-beta-lactamase and inactivate the protein; inhibitors of this type are optimal for any new inhibitor that could be used in the clinic.