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  • Contribution of direct InhA inhibitors to novel drug regimens in a mouse model of tuberculosis [Elektronski vir]
    Encinas, Lourdes ...
    Isoniazid is an important first-line medicine to treat tuberculosis (TB). Isoniazid resistance increases the risk of poor treatment outcomes and development of multidrug resistance, and is driven ... primarily by mutations involving katG, encoding the prodrug-activating enzyme, rather than its validated target, InhA. The chemical tractability of InhA has fostered efforts to discover direct inhibitors of InhA (DIIs). In this study, we bridge the gap in understanding the potential contribution of DIIs to novel combination regimens and demonstrate a clear distinction of DIIs, like GSK693 and the newly described GSK138, from isoniazid, based on activity against clinical isolates and contribution to novel drug regimens. The results suggest that DIIs, specifically GSK138 and GSK693, could be promising partners in novel drug regimens, including those used against isoniazid-resistant TB, potentially enhancing their efficacy and/or preventing the selection of resistant mutants and supporting the continued exploration of InhA as a promising target for TB drug development.
    Source: Antimicrobial agents and chemotherapy [Elektronski vir]. - ISSN 1098-6596 (Vol. 68, iss. 11, 2024, 17 str.)
    Type of material - e-article ; adult, serious
    Publish date - 2024
    Language - english
    COBISS.SI-ID - 209594883

    Link(s):

    https://journals.asm.org/doi/10.1128/aac.00357-24
    https://journals.asm.org/doi/epub/10.1128/aac.00357-24
    Repository of the University of Ljubljana – RUL
    DOI

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