New Antibacterials Against D,D- and L,D-Transpeptidases

Unmet need
b-lactam antibacterial agents target peptidoglycan biosynthesis and are used for treatment of infection, but have been ineffective in treatment of Tuberculosis (TB). This lack of activity has been attributed to the presence of b-lactamase and limited penetration of the thick mycolate coat. Thus, new generation of antibacterial agents to treat TB, a disease that causes more deaths worldwide than any other infectious disease, are urgently needed.

Technology overview
Johns Hopkins researchers have identified novel b-lactam antibacterials that contain a bicyclic penem core. The current antibacterials are poor substrates for β-lactamases, and can also inhibit non-classical transpeptidases, l,d-transpeptidases, that generate the majority of linkages in the peptidoglycan of mycobacteria. They verified that these compounds bind l,d-transpeptidases of several bacterial pathogens, using kinetics and x-ray structural studies. The pathogens include Gram-positive, Gram-negative and acid-fast bacteria.
 
Stage of development
Discovery
 
Publications
Kumar P et al. Nat Chem Biol 13(1), 54–61, 2017
 

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