Thienothiazolocarboxamides: rapidly cidal agents causing catastrophic thiol collapse in Mycobacterium tuberculosis.

Thienothiazolocarboxamides rapidly kill Mycobacterium tuberculosis in macrophages under both replicating and non-replicating conditions, linked to EthA-dependent thiol collapse.

• Why it matters: The need is for antituberculosis agents with replication-independent killing and a clear mechanism that could help shorten tuberculosis chemotherapy duration.
• What they did: TTCs were identified in a whole-cell screen, then tested for rapid cidal activity; resistance mapped to loss of EthA, and EthA activation was assessed via mycothiol adducts and RNAseq.
• The result: EthA-mediated activation generates mycothiol adducts and RNAseq profiles matching the fungal mycotoxins patulin and nidulalin A, implying a replication-independent thiol-reactive mechanism.

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