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The first wide-scal...
The first wide-scale drug repurposing screen using the Prestwick Chemical Library (1200 bioactive molecules) against Neisseria gonorrhoeae identifies high in vitro activity of auranofin and many additional drugs
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- Foerster, Sunniva (författare)
- WHO Collaborating Centre for Gonorrhoea and other STIs, Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Heidelberg, Germany
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- Gustafsson, Tomas N. (författare)
- Umeå universitet,Institutionen för klinisk mikrobiologi,Sunderby Research Unit, Umeå University, Umeå, Sweden
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- Rita Brochado, Anna (författare)
- European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Heidelberg, Germany
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- Desilvestro, Valentino (författare)
- World Trade Institute (WTI), University of Bern, Bern, Switzerland
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- Typas, Athanasios (författare)
- European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Heidelberg, Germany
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- Unemo, Magnus, 1970- (författare)
- Örebro universitet,Institutionen för medicinska vetenskaper,Region Örebro län,WHO Collaborating Centre for Gonorrhoea and other STIs, Department of Laboratory Medicine
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(creator_code:org_t)
- 2020-01-28
- 2020
- Engelska.
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Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - : Wiley-Blackwell Publishing Inc.. - 0903-4641 .- 1600-0463. ; 128:3, s. 242-250
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- Treatment options for gonorrhoea are scarce. Drug repurposing of bioactive molecules approved for other conditions might therefore be of value. We developed a method for wide-scale, systematic drug repurposing screen to identify molecules with activity against Neisseria gonorrhoeae and screened the Prestwick Chemical Library (1200 FDA-approved drugs). As a proof-of-concept, we further examined one promising and interesting screening hit (auranofin; antirheumatic agent). Three WHO gonococcal reference strains (WHO F, O, P) were used for the Library screening. The strains were grown in presence of a fixed concentration of the library drugs in 384-well plates for 12 hours and the remaining bacterial respiration, to reflect growth, was then quantitatively measured using optical density (OD) 450 nm and a resazurin assay. The activity of auranofin was further examined using in vitro susceptibility testing (minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC)) against genetically diverse antimicrobial-resistant N. gonorrhoeae strains and time-kill assays. Sixty-eight molecules significantly inhibited bacterial growth of WHO F, O and, P. Auranofin showed potent in vitro bactericidal activity (in MIC-, MBC-, and time-kill assays) against four WHO reference strains. No cross resistance between auranofin and any antimicrobial currently or previously used for gonorrhoea treatment was found when examining 51 selected antimicrobial-resistant gonococcal strains. In conclusion, this is the first wide-scale systematic screening effort for repurposing drugs for future treatment of gonorrhoea. Additional studies examining mechanism(s) of action, resistance development, in vivo anti-gonococcal activity, and pharmacokinetics/pharmacodynamics for gonococcal infections of auranofin and several other significant screening hits would be valuable.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Infektionsmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Infectious Medicine (hsv//eng)
Nyckelord
- Gonorrhoea
- Prestwick Chemical Library
- antimicrobial
- auranofin
- high-throughput screen
- treatment
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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