What is it about?
We use an old class of drugs (Beta lactams) and show their inhibition of L,D-transpeptidase which is important in mycobacteria. We performed mechanistic characterization of compounds and designed and tested some new potent antibacterials.
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Why is it important?
TB treatment needs new drugs and yet beta lactams have not been widely used to treat this disease. We provide a better understanding of how the bet-lactams function against the enzyme L,D-transpeptidase. We solved many crystal structures and tested carbapems in vivo. We also designed new compounds. We also identified L,D-transpeptidases in ESKAPE pathogens.
Perspectives
My tiny contribution to this work was the molecular features that were used in the design of the new carbapenems. They are derived from our earlier machine learning work on whole cell active compounds vs Mtb. Having being involved in this project for several years I can honestly say it was a major effort to pull this together and Gyanu deserves huge credit.
Dr Sean Ekins
Collaborations in Chemistry
I contributed to molecular and mechanistic understanding of old and newly evolved carbapenems in inhibition of L,D-transpeptidases from M. tuberculosis and ESKAPE pathogens through several biophysical and biochemical approaches. It was a great team effort of many researchers including the most from Gyanu, that lead to the development of new antibiotics towards treatment of drug-resistant pathogens including TB.
Dr Pankaj Kumar
Jamia Hamdard
Read the Original
This page is a summary of: Non-classical transpeptidases yield insight into new antibacterials, Nature Chemical Biology, November 2016, Nature,
DOI: 10.1038/nchembio.2237.
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