Science Pool

Identification of β-Lactams Active Against Mycobacterium Tuberculosis

Posted by Evotec on Mar 10, 2022 7:02:39 PM

Rising antimicrobial resistance challenges our ability to combat bacterial infections. The problem is acute for tuberculosis (TB), the leading cause of death from infection before COVID-19.

Here, we developed a framework for multiple pharmaceutical companies to share proprietary information and compounds with multiple laboratories in the academic and government sectors for a broad examination of the ability of β-lactams to kill Mycobacterium tuberculosis (Mtb). In the TB Drug Accelerator (TBDA), a consortium organized by the Bill & Melinda Gates Foundation, individual pharmaceutical companies collaborate with academic screening laboratories.

  • In this paper we describe strategies used to prioritize thousands of β-lactams from multiple companies into a small test set for further characterization.
  • In a striking contrast to historical expectation, 18% of β-lactams screened were active against Mtb, many without a β-lactamase inhibitor.
  • One potent cephaloporin was active in Mtb-infected mice.
The steps outlined here can serve as a blueprint for multiparty, intra- and intersector collaboration in the development of anti-infective agents.

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Tags: Articles & Whitepapers, Hit & Target ID/Validation, Anti-Infectives