Development and validation of a high-throughput anti-Wolbachia whole-cell screen: a route to macrofilaricidal drugs against onchocerciasis and lymphatic filariasis

J Biomol Screen. 2015 Jan;20(1):64-9. doi: 10.1177/1087057114551518. Epub 2014 Oct 2.


There is an urgent need to develop new, safe, and affordable macrofilaricidal drugs for onchocerciasis and lymphatic filariasis treatment and control. The Anti-Wolbachia Consortium (A·WOL) aims to provide a novel treatment with macrofilaricidal activity by targeting the essential bacterial symbiont Wolbachia. The consortium is currently screening a diverse range of compounds to find new chemical space to drive this drug discovery initiative and address this unmet demand. To increase the throughput and capacity of the A·WOL cell-based screen, we have developed a 384-well format assay using a high-content imaging system (Operetta) in conjunction with optimized Wolbachia growth dynamics in the C6/36 Aedes albopictus mosquito cell line. This assay uses texture analysis of cells stained with SYTO 11 as a direct measure of bacterial load. This validated assay has dramatically increased the capacity and throughput of the A·WOL compound library screening program 25-fold, enriching the number of new anti-Wolbachia hits identified for further development as potential macrofilaricides for onchocerciasis and lymphatic filariasis.

Keywords: cell-based assays; fluorescence methods; high-content screening; phenotypic drug discovery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Anti-Bacterial Agents / therapeutic use
  • Antinematodal Agents / pharmacology*
  • Antinematodal Agents / therapeutic use
  • Cell Line
  • Dose-Response Relationship, Drug
  • Drug Discovery / methods*
  • Drug Discovery / standards
  • Elephantiasis, Filarial / drug therapy
  • High-Throughput Screening Assays / methods*
  • High-Throughput Screening Assays / standards
  • Humans
  • Neglected Diseases / drug therapy
  • Onchocerca / microbiology
  • Onchocerciasis / drug therapy
  • Reproducibility of Results
  • Wolbachia / drug effects*
  • Wolbachia / physiology*


  • Anti-Bacterial Agents
  • Antinematodal Agents