Researchers have begun developing new compounds to attack previously untargeted bacterial enzymes, present in cases of drug-resistant infections such as multidrug-resistant tuberculosis (MDR-TB).
Published in the journal Nature Chemical Biology, the study suggests that antibiotic drugs specifically targeting the recently identified LD-transpeptidase enzyme, which is needed to build bacterial cell walls in some bacteria, could potentially cure many antibiotic-resistant infections.
The researchers first analysed the enzyme’s detailed molecular structure using protein X-ray crystallography. The findings enabled the team to develop compounds in the carbapenem group, a subclass of the beta-lactam antibiotics that bind to the LD-transpeptidase enzyme. They found that two live bacterial cultures of the carbapenems were shown to stop the enzyme's wall-building activity.
Researchers then tested two carbapenems in vivo by infecting two mice with tuberculosis (TB), and found that even without use of traditional antibiotic TB treatments, the new carbapenems, specifically biapenem, cured mice of TB infection. The research team are now in the process of beginning clinical trials to test the efficacy and safety of the compounds for use as a treatment for TB patients.