Development and Validation of a High-Throughput Anti-Wolbachia Whole-Cell Screen: A Route to Macrofilaricidal Drugs against Onchocerciasis and Lymphatic Filariasis

Rachel Clare; Darren A.N. Cook; Kelly Johnston; Louise Ford; Steve Ward; Mark Taylor

doi:10.1177/1087057114551518

Development and Validation of a High-Throughput Anti-Wolbachia Whole-Cell Screen: A Route to Macrofilaricidal Drugs against Onchocerciasis and Lymphatic Filariasis

Rachel Clare, Darren A.N. Cook, Kelly Johnston, Louise Ford, Steve Ward, Mark Taylor

Liverpool School of Tropical Medicine

Research output: Contribution to journal › Article › peer-review

41 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	64-69
Number of pages	6
Journal	Journal of Biomolecular Screening
Volume	20
Issue number	1
DOIs	https://doi.org/10.1177/1087057114551518
Publication status	Published - 2 Oct 2014

Keywords

cell-based assays
fluorescence methods
high-content screening
phenotypic drug discovery

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title = "Development and Validation of a High-Throughput Anti-Wolbachia Whole-Cell Screen: A Route to Macrofilaricidal Drugs against Onchocerciasis and Lymphatic Filariasis",

abstract = "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.",

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AU - Ford, Louise

AU - Ward, Steve

AU - Taylor, Mark

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AB - 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.

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Development and Validation of a High-Throughput Anti-Wolbachia Whole-Cell Screen: A Route to Macrofilaricidal Drugs against Onchocerciasis and Lymphatic Filariasis

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Keywords

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