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

• Published in: SLAS discovery 2019-06, Vol.24 (5), p.537-547
• Main Authors: Clare, Rachel H., Clark, Roger, Bardelle, Catherine, Harper, Paul, Collier, Matthew, Johnston, Kelly L., Plant, Helen, Plant, Darren, McCall, Eileen, Slatko, Barton E., Cantin, Lindsey, Wu, Bo, Ford, Louise, Murray, David, Rich, Kirsty, Wigglesworth, Mark, Taylor, Mark J., Ward, Stephen A.
• Format: Article
• Language: English
• Subjects: 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; Original Research; Wolbachia - drug effects; Wolbachia - pathogenicity; Wolbachia - ultrastructure
• ISSN: 2472-5552; 2472-5560
• DOI: 10.1177/2472555219838341

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.