A cell-based screening platform identifies novel mosquitocidal toxins

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Pesticides currently in widespread use often lack species specificity and also become less effective as resistance emerges. Consequently, there is a pressing need to develop novel agents that are narrowly targeted and safe to humans. A cell-based screening platform was designed to discover compounds that are lethal to mosquito (Anopheles and Aedes) cells but show little or no activity against other insect (Drosophila) or human cell lines. Mosquito-specific, aqueous-stable cytotoxins were recovered at rare frequencies. Three of these were profiled for structure-activity relationships and also assessed in whole-animal toxicity assays. In at least one test case, species-specific cytotoxicity seen in culture effectively translated to the whole-animal level, with potent toxicity against Anopheles yet none against Drosophila. Therefore, this initiative has the potential to advance novel mosquitocidal agents and, in a broader sense, could establish a versatile platform for developing customized pesticides that selectively target other disease vectors as well.

Original languageEnglish (US)
Pages (from-to)688-694
Number of pages7
JournalJournal of Biomolecular Screening
Volume18
Issue number6
DOIs
StatePublished - Jul 2013

Fingerprint

Anopheles
Culicidae
Pesticides
Drosophila
Toxicity
Screening
Animals
Disease Vectors
Species Specificity
Aedes
Cytotoxins
Structure-Activity Relationship
Cytotoxicity
Cell culture
Insects
Assays
Cells
Cell Line

Keywords

  • agricultural
  • animal health
  • cell-based assays
  • high-content screening
  • phenotypic drug discovery

ASJC Scopus subject areas

  • Analytical Chemistry
  • Drug Discovery
  • Pharmacology
  • Biochemistry
  • Molecular Medicine
  • Biotechnology

Cite this

A cell-based screening platform identifies novel mosquitocidal toxins. / O'Neal, Melissa A.; Posner, Bruce A.; Coates, Craig J.; Abrams, John M.

In: Journal of Biomolecular Screening, Vol. 18, No. 6, 07.2013, p. 688-694.

Research output: Contribution to journalArticle

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