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Updated: Jan 11, 2026

Preparation of Mycobacterium Tuberculosis Culture Filtrate to Understand TB Pathogenesis
Published on: March 28, 2025
Mutations in the Esx-3 secretion system confer resistance to multiple chemical scaffolds in Mycobacterium
Theresa O'Malley1, Matthew B McNeil1,2, Devon Dennison1
1TB Discovery Research, Infectious Disease Research Institute, Seattle, WA, USA.
Abstract:
We determined the mechanism of resistance to seven chemical series with potent activity against Mycobacterium tuberculosis. Resistant mutants were isolated against the aminothiazoles, phenylhydrazones, 8-hydroxyquinolines, nitazoxanides, phenyl alkylimidazoles, morpholino thiophenes and trifluoromethyl pyrimidinones. We demonstrated that mutations in several components of the Esx-3 type VII secretion system (EccA3, EccB3, EccC3 and EccD3) conferred resistance to these disparate scaffolds. We conclude that mutations in Esx-3 are a common mechanism of resistance to anti-tubercular agents, which may have clinical relevance for new drugs.
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