High-throughput screening system for antimycobacterial compounds using in vitro infected cells: construction and application to compounds in the Ōmura Natural Compound Library
Rattachement africain : jp. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
ABSTRACT The global increase in multidrug-resistant tuberculosis strains poses a major threat; consequently, there is an urgent need to identify and develop novel drugs. We have previously presented a simple fibroblast assay (SFA) screening method that enables the simultaneous assessment of antibacterial activity and cytotoxicity toward host cells. This method was developed based on our finding that live (but not dead) Mycobacterium tuberculosis bacilli exhibit cytotoxic activity against human lung fibroblasts, and that this cytotoxicity, which is proportional to the number of viable bacterial cells, is inhibited by known antimycobacterial drugs. While conventional methods to measure M. tuberculosis growth require 2–4 weeks to detect antibacterial activity; the SFA method enables detection within 2–3 days and can detect compounds that are active within host cells. Here, we applied high-throughput screening, based on assessment of cytotoxicity, to identify candidate antimycobacterial agents. In parallel, by comparing the direct antibacterial activity of compounds in liquid medium (using the broth dilution test) with that observed via SFA, we developed a new SFA-based screening system to select compounds with low cytotoxicity that are active outside or inside the host cells. Using this dual system, we screened 742 compounds from the Ōmura Natural Compound Library (Kitasato University, Japan), with 62 hits. Of these, 19 were excluded owing to their toxicity, and six exhibited antibacterial activity only via SFA screening. Four promising antimycobacterial candidates with no cytotoxicity at the 10 μg/mL threshold—aridicin A, lankamycin, streptovaricin, and lariatin A—were identified. This novel system supports the rapid identification of low-cytotoxicity antimycobacterial compounds that are active inside or outside the host cells. IMPORTANCE This screening system, comprising the simple fibroblast assay (SFA) and broth dilution test (BDT), effectively identifies low-cytotoxicity compounds that exhibit antimycobacterial activity inside or outside the host cells.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé, mais le titre doit être comparé manuellement.
- Titre Crossref
- High-throughput screening system for antimycobacterial compounds using <i>in vitro</i> infected cells: construction and application to compounds in the Ōmura Natural Compound Library
- Date Crossref
- 04/08/2026
- Éditeur
- American Society for Microbiology
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Nagoya City University pays non établi dans la noticeUniversité ou école supérieure
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Japan Anti Tuberculosis Association pays non établi dans la noticeInstitution
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Kitasato University Ōmura Satoshi Memorial Institute pays non établi dans la noticeUniversité ou école supérieure
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Okayama University pays non établi dans la noticeUniversité ou école supérieure
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Graduate School of Pharmaceutical Sciences Department of Hygienic Chemistry pays non établi dans la noticeUniversité ou école supérieure
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The Research Institute of Tuberculosis Department of Mycobacterium Reference and Research pays non établi dans la noticeStructure de recherche
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Graduate School of Infection Control Sciences pays non établi dans la noticeUniversité ou école supérieure
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Graduate School of Medicine Department of Oral Microbiology pays non établi dans la noticeUniversité ou école supérieure
Nagoya City University, Japan Anti Tuberculosis Association et Ōmura Satoshi Memorial Institute — Kitasato University, avec 5 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.