A carbapenem molecule enters a beta-lactamase enzyme (blue arrow), which alters its structure. The ineffective molecule is then released (orange arrow).UNIVERSITY OF BRISTOL
Carbapenems, beta-lactam antibiotics similar to penicillin, have been used for more than 30 years as treatments of last resort against drug-resistant strains of Escherichia coli, Pseudomonas aeruginosa, and other pathogens. But now, bacterial resistance against carbapenems is also on the rise.
Researchers at the University of Bristol in the U.K. have applied an in silico method to model how carbapenems interact with bacterial beta-lactamase enzymes. The technique, reported this month in Chemical Communications, may aid both the development and deployment of carbapenem antibiotics.
Resistance to penicillins, carbapenems, and other beta-lactam antibiotics depends on how quickly a bacterial beta-lactamase releases the broken-down antibiotic. Because carbapenems generally form more stable complexes with beta-lactamases, they act as enzymatic inhibitors. A simulation method called quantum mechanics/molecular mechanics (QM/MM), whose ...
