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Mycobacterium tuberculosis virulence inhibitors discovered by Mycobacterium marinum high-throughput screening
Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
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2019 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 26Article in journal (Refereed) Published
Abstract [en]

High-throughput screening facilities do not generally support biosafety level 3 organisms such as Mycobacterium tuberculosis. To discover not only antibacterials, but also virulence inhibitors with either bacterial or host cell targets, an assay monitoring lung fibroblast survival upon infection was developed and optimized for 384-plate format and robotic liquid handling. By using Mycobacterium marinum as surrogate organism, 28,000 compounds were screened at biosafety level 2 classification, resulting in 49 primary hits. Exclusion of substances with unfavourable properties and known antimicrobials resulted in 11 validated hits of which 7 had virulence inhibiting properties and one had bactericidal effect also in wild type Mycobacterium tuberculosis. This strategy to discover virulence inhibitors using a model organism in high-throughput screening can be a valuable tool for other researchers working on drug discovery against tuberculosis and other biosafety level 3 infectious agents.

Place, publisher, year, edition, pages
Nature Publishing Group, 2019. Vol. 9, article id 26
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Infectious Medicine
Identifiers
URN: urn:nbn:se:umu:diva-155761DOI: 10.1038/s41598-018-37176-4ISI: 000455352400009PubMedID: 30631100OAI: oai:DiVA.org:umu-155761DiVA, id: diva2:1283164
Funder
Swedish Research CouncilVINNOVAThe Kempe FoundationsAvailable from: 2019-01-28 Created: 2019-01-28 Last updated: 2019-01-28Bibliographically approved

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Edström, Isabel

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