Development and validation of a high-throughput anti-Wolbachia whole-cell screen: a route to macrofilaricidal drugs against onchocerciasis and lymphatic filariasis.
Identifieur interne : 001F08 ( Main/Exploration ); précédent : 001F07; suivant : 001F09Development and validation of a high-throughput anti-Wolbachia whole-cell screen: a route to macrofilaricidal drugs against onchocerciasis and lymphatic filariasis.
Auteurs : Rachel H. Clare [Royaume-Uni] ; Darren A N. Cook [Royaume-Uni] ; Kelly L. Johnston [Royaume-Uni] ; Louise Ford [Royaume-Uni] ; Stephen A. Ward [Royaume-Uni] ; Mark J. Taylor [Royaume-Uni]Source :
- Journal of biomolecular screening [ 1552-454X ] ; 2015.
Descripteurs français
- KwdFr :
- Animaux, Antibactériens (pharmacologie), Antibactériens (usage thérapeutique), Antihelminthiques antinématodes (pharmacologie), Antihelminthiques antinématodes (usage thérapeutique), Découverte de médicament (), Découverte de médicament (normes), Filariose lymphatique (traitement médicamenteux), Humains, Lignée cellulaire, Maladies négligées (traitement médicamenteux), Onchocerca (microbiologie), Onchocercose (traitement médicamenteux), Relation dose-effet des médicaments, Reproductibilité des résultats, Tests de criblage à haut débit (), Tests de criblage à haut débit (normes), Wolbachia (), Wolbachia (physiologie).
- MESH :
- microbiologie : Onchocerca.
- normes : Découverte de médicament, Tests de criblage à haut débit.
- pharmacologie : Antibactériens, Antihelminthiques antinématodes.
- physiologie : Wolbachia.
- traitement médicamenteux : Filariose lymphatique, Maladies négligées, Onchocercose.
- usage thérapeutique : Antibactériens, Antihelminthiques antinématodes.
- Animaux, Découverte de médicament, Humains, Lignée cellulaire, Relation dose-effet des médicaments, Reproductibilité des résultats, Tests de criblage à haut débit, Wolbachia.
English descriptors
- KwdEn :
- 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).
- MESH :
- chemical , pharmacology : Anti-Bacterial Agents, Antinematodal Agents.
- chemical , therapeutic use : Anti-Bacterial Agents, Antinematodal Agents.
- drug effects : Wolbachia.
- drug therapy : Elephantiasis, Filarial, Neglected Diseases, Onchocerciasis.
- methods : Drug Discovery, High-Throughput Screening Assays.
- microbiology : Onchocerca.
- physiology : Wolbachia.
- standards : Drug Discovery, High-Throughput Screening Assays.
- Animals, Cell Line, Dose-Response Relationship, Drug, Humans, Reproducibility of Results.
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.
DOI: 10.1177/1087057114551518
PubMed: 25278497
Affiliations:
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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.</div></front></TEI><affiliations><list><country><li>Royaume-Uni</li></country></list><tree><country name="Royaume-Uni"><noRegion><name sortKey="Clare, Rachel H" sort="Clare, Rachel H" uniqKey="Clare R" first="Rachel H" last="Clare">Rachel H. Clare</name></noRegion><name sortKey="Cook, Darren A N" sort="Cook, Darren A N" uniqKey="Cook D" first="Darren A N" last="Cook">Darren A N. Cook</name><name sortKey="Ford, Louise" sort="Ford, Louise" uniqKey="Ford L" first="Louise" last="Ford">Louise Ford</name><name sortKey="Johnston, Kelly L" sort="Johnston, Kelly L" uniqKey="Johnston K" first="Kelly L" last="Johnston">Kelly L. Johnston</name><name sortKey="Taylor, Mark J" sort="Taylor, Mark J" uniqKey="Taylor M" first="Mark J" last="Taylor">Mark J. Taylor</name><name sortKey="Ward, Stephen A" sort="Ward, Stephen A" uniqKey="Ward S" first="Stephen A" last="Ward">Stephen A. Ward</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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