Development of a High-Throughput Cytometric Screen to Identify Anti- Wolbachia Compounds: The Power of Public-Private Partnership

SLAS Discov. 2019 Jun;24(5):537-547. doi: 10.1177/2472555219838341. Epub 2019 Apr 8.

Abstract

The Anti- Wolbachia (A·WOL) consortium at the Liverpool School of Tropical Medicine (LSTM) has partnered with the Global High-Throughput Screening (HTS) Centre at AstraZeneca to create the first anthelmintic HTS for neglected tropical diseases (NTDs). The A·WOL consortium aims to identify novel macrofilaricidal drugs targeting the essential bacterial symbiont ( Wolbachia) of the filarial nematodes causing onchocerciasis and lymphatic filariasis. Working in collaboration, we have validated a robust high-throughput assay capable of identifying compounds that selectively kill Wolbachia over the host insect cell. We describe the development and validation process of this complex, phenotypic high-throughput assay and provide an overview of the primary outputs from screening the AstraZeneca library of 1.3 million compounds.

Keywords: acumen; high-throughput screening; lymphatic filariasis; neglected tropical diseases; onchocerciasis; phenotypic screening.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Cell Culture Techniques / methods
  • Drug Discovery
  • Elephantiasis, Filarial / drug therapy
  • High-Throughput Screening Assays*
  • Host-Pathogen Interactions / drug effects*
  • Humans
  • Image Cytometry
  • Onchocerciasis / drug therapy
  • Wolbachia / drug effects*
  • Wolbachia / pathogenicity
  • Wolbachia / ultrastructure

Substances

  • Anti-Bacterial Agents