Agent Helps Carbapenems Fight Bacterial Resistance

Scientists have identified a natural product that inhibits an enzyme that bacteria use to disable carbapenem β-lactams, antibiotics of last resort for pneumonia and other infections. Bacteria resist carbapenems by expressing serine- or metallo-β-lactamases that destroy the β-lactam ring the antibiotics use to kill them. Several serine-β-lactamase inhibitors are used as antibiotic adjuvants, agents coadministered with antibiotics to fight infection. But no metallo-β-lactamase inhibitors have been identified or approved. Now, Gerard D. Wright of McMaster University, in Ontario, and coworkers have found such an inhibitor by screening an in-house collection of microbial natural products for antibiotic activity against resistant bacteria (Nature 2014, DOI: 10.1038/nature13445). The agent, the fungal natural product aspergillomarasmine A, inhibits metallo-β-lactamase and related enzymes. In experiments on mice infected with a lethal dose of pneumonia bacteria with metallo-β-lactamase-based antibiotic resistance, a carbapenem drug or aspergillomarasmine A failed to protect the mice. But when administered together, they caused 95% of treated mice to survive. Aspergillomarasmine A could help in the fight against enzymes “that have become rapidly global and result in significant human morbidity, particularly in developing countries,” the researchers note.