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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

Clare, Rachel ORCID: https://orcid.org/0000-0002-3945-0530, Cook, Darren, Johnston, Kelly, Ford, Louise, Ward, Stephen ORCID: https://orcid.org/0000-0003-2331-3192 and Taylor, Mark (2015) 'Development and Validation of a High-Throughput Anti-Wolbachia Whole-Cell Screen: A Route to Macrofilaricidal Drugs against Onchocerciasis and Lymphatic Filariasis'. Journal of Biomolecular Screening, Vol 20, Issue 1, pp. 64-69.

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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.

Item Type: Article
Subjects: QU Biochemistry > Cells and Genetics > QU 350 Cellular structures
QV Pharmacology > Anti-Inflammatory Agents. Anti-Infective Agents. Antineoplastic Agents > QV 253 Anthelmintics
QV Pharmacology > QV 4 General works
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 880 Filariasis and related conditions (General)
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 885 Onchocerciasis
Faculty: Department: Biological Sciences > Department of Tropical Disease Biology
Digital Object Identifer (DOI): https://doi.org/10.1177/1087057114551518
Depositing User: Lynn Roberts-Maloney
Date Deposited: 23 Jan 2015 16:37
Last Modified: 06 Feb 2018 13:08
URI: https://archive.lstmed.ac.uk/id/eprint/4790

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