Abstract:
: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.
journal_name
Sci Repjournal_title
Scientific reportsauthors
Tükenmez H,Edström I,Ummanni R,Fick SB,Sundin C,Elofsson M,Larsson Cdoi
10.1038/s41598-018-37176-4subject
Has Abstractpub_date
2019-01-10 00:00:00pages
26issue
1issn
2045-2322pii
10.1038/s41598-018-37176-4journal_volume
9pub_type
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