Rapid Identification of Antifungal Compounds against Exserohilum rostratum Using High Throughput Drug Repurposing Screens

Wei Sun, Yoon Dong Park, Janyce A. Sugui, Annette Fothergill, Noel Southall, Paul Shinn, John C. McKew, Kyung J. Kwon-Chung, Wei Zheng, Peter R. Williamson

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

A recent large outbreak of fungal infections by Exserohilum rostratum from contaminated compounding solutions has highlighted the need to rapidly screen available pharmaceuticals that could be useful in therapy. The present study utilized two newly-developed high throughput assays to screen approved drugs and pharmaceutically active compounds for identification of potential antifungal agents. Several known drugs were found that have potent effects against E. rostratum including the triazole antifungal posaconazole. Posaconazole is likely to be effective against infections involving septic joints and may provide an alternative for refractory central nervous system infections. The anti-E. rostratum activities of several other drugs including bithionol (an anti-parasitic drug), tacrolimus (an immunosuppressive agent) and floxuridine (an antimetabolite) were also identified from the drug repurposing screens. In addition, activities of other potential antifungal agents against E. rostratum were excluded, which may avoid unnecessary therapeutic trials and reveals the limited therapeutic alternatives for this outbreak. In summary, this study has demonstrated that drug repurposing screens can be quickly conducted within a useful time-frame. This would allow clinical implementation of identified alternative therapeutics and should be considered as part of the initial public health response to new outbreaks or rapidly-emerging microbial pathogens.

Original languageEnglish (US)
Article numbere70506
JournalPLoS One
Volume8
Issue number8
DOIs
StatePublished - Aug 21 2013

Fingerprint

Drug Repositioning
Exserohilum
Throughput
drugs
Disease Outbreaks
Pharmaceutical Preparations
Antifungal Agents
therapeutics
Bithionol
Floxuridine
floxuridine
Antimetabolites
Central Nervous System Infections
Triazoles
Mycoses
Tacrolimus
Therapeutics
Immunosuppressive Agents
tacrolimus
infection

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Sun, W., Park, Y. D., Sugui, J. A., Fothergill, A., Southall, N., Shinn, P., ... Williamson, P. R. (2013). Rapid Identification of Antifungal Compounds against Exserohilum rostratum Using High Throughput Drug Repurposing Screens. PLoS One, 8(8), [e70506]. https://doi.org/10.1371/journal.pone.0070506

Rapid Identification of Antifungal Compounds against Exserohilum rostratum Using High Throughput Drug Repurposing Screens. / Sun, Wei; Park, Yoon Dong; Sugui, Janyce A.; Fothergill, Annette; Southall, Noel; Shinn, Paul; McKew, John C.; Kwon-Chung, Kyung J.; Zheng, Wei; Williamson, Peter R.

In: PLoS One, Vol. 8, No. 8, e70506, 21.08.2013.

Research output: Contribution to journalArticle

Sun, W, Park, YD, Sugui, JA, Fothergill, A, Southall, N, Shinn, P, McKew, JC, Kwon-Chung, KJ, Zheng, W & Williamson, PR 2013, 'Rapid Identification of Antifungal Compounds against Exserohilum rostratum Using High Throughput Drug Repurposing Screens', PLoS One, vol. 8, no. 8, e70506. https://doi.org/10.1371/journal.pone.0070506
Sun, Wei ; Park, Yoon Dong ; Sugui, Janyce A. ; Fothergill, Annette ; Southall, Noel ; Shinn, Paul ; McKew, John C. ; Kwon-Chung, Kyung J. ; Zheng, Wei ; Williamson, Peter R. / Rapid Identification of Antifungal Compounds against Exserohilum rostratum Using High Throughput Drug Repurposing Screens. In: PLoS One. 2013 ; Vol. 8, No. 8.
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