Mycobacterium tuberculosis virulence inhibitors discovered by Mycobacterium marinum high-throughput screening

Autor: Christer Larsson, Charlotta Sundin, Ramesh Ummanni, Hasan Tükenmez, Mikael Elofsson, Stina Berglund Fick, Isabel Edström
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: Scientific Reports, Vol 9, Iss 1, Pp 1-9 (2019)
Scientific Reports
ISSN: 2045-2322
DOI: 10.1038/s41598-018-37176-4
Popis: 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.
Databáze: OpenAIRE
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