A Cell-Based Screen Reveals that the Albendazole Metabolite, Albendazole Sulfone, Targets Wolbachia
Identifieur interne : 000235 ( France/Analysis ); précédent : 000234; suivant : 000236A Cell-Based Screen Reveals that the Albendazole Metabolite, Albendazole Sulfone, Targets Wolbachia
Auteurs : Laura R. Serbus [États-Unis] ; Frederic Landmann [États-Unis] ; Walter M. Bray [États-Unis] ; Pamela M. White [États-Unis] ; Jordan Ruybal [États-Unis] ; R. Scott Lokey [États-Unis] ; Alain Debec [France] ; William Sullivan [États-Unis]Source :
- PLoS Pathogens [ 1553-7366 ] ; 2012.
Abstract
Url:
DOI: 10.1371/journal.ppat.1002922
PubMed: 23028321
PubMed Central: 3447747
Affiliations:
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White</name><affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Molecular, Cell and Developmental Biology, University of California, Santa Cruz, California, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Molecular, Cell and Developmental Biology, University of California, Santa Cruz, California</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Ruybal, Jordan" sort="Ruybal, Jordan" uniqKey="Ruybal J" first="Jordan" last="Ruybal">Jordan Ruybal</name><affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Molecular, Cell and Developmental Biology, University of California, Santa Cruz, California, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Molecular, Cell and Developmental Biology, University of California, Santa Cruz, California</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Lokey, R Scott" sort="Lokey, R Scott" uniqKey="Lokey R" first="R. 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Serbus</name><affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Molecular, Cell and Developmental Biology, University of California, Santa Cruz, California, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Molecular, Cell and Developmental Biology, University of California, Santa Cruz, California</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Landmann, Frederic" sort="Landmann, Frederic" uniqKey="Landmann F" first="Frederic" last="Landmann">Frederic Landmann</name><affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Molecular, Cell and Developmental Biology, University of California, Santa Cruz, California, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Molecular, Cell and Developmental Biology, University of California, Santa Cruz, California</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Bray, Walter M" sort="Bray, Walter M" uniqKey="Bray W" first="Walter M." last="Bray">Walter M. Bray</name><affiliation wicri:level="2"><nlm:aff id="aff2"><addr-line>Department of Chemistry and Biochemistry, University of California, Santa Cruz, California, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Chemistry and Biochemistry, University of California, Santa Cruz, California</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="White, Pamela M" sort="White, Pamela M" uniqKey="White P" first="Pamela M." last="White">Pamela M. White</name><affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Molecular, Cell and Developmental Biology, University of California, Santa Cruz, California, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Molecular, Cell and Developmental Biology, University of California, Santa Cruz, California</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Ruybal, Jordan" sort="Ruybal, Jordan" uniqKey="Ruybal J" first="Jordan" last="Ruybal">Jordan Ruybal</name><affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Molecular, Cell and Developmental Biology, University of California, Santa Cruz, California, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Molecular, Cell and Developmental Biology, University of California, Santa Cruz, California</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Lokey, R Scott" sort="Lokey, R Scott" uniqKey="Lokey R" first="R. Scott" last="Lokey">R. Scott Lokey</name><affiliation wicri:level="2"><nlm:aff id="aff2"><addr-line>Department of Chemistry and Biochemistry, University of California, Santa Cruz, California, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Chemistry and Biochemistry, University of California, Santa Cruz, California</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Debec, Alain" sort="Debec, Alain" uniqKey="Debec A" first="Alain" last="Debec">Alain Debec</name><affiliation wicri:level="3"><nlm:aff id="aff3"><addr-line>Polarity and Morphogenesis Group, Jacques Monod Institute, CNRS, University Paris Diderot, UPMC Bâtiment Buffon, Paris, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Polarity and Morphogenesis Group, Jacques Monod Institute, CNRS, University Paris Diderot, UPMC Bâtiment Buffon, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Sullivan, William" sort="Sullivan, William" uniqKey="Sullivan W" first="William" last="Sullivan">William Sullivan</name><affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Molecular, Cell and Developmental Biology, University of California, Santa Cruz, California, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Molecular, Cell and Developmental Biology, University of California, Santa Cruz, California</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author></analytic><series><title level="j">PLoS Pathogens</title><idno type="ISSN">1553-7366</idno><idno type="eISSN">1553-7374</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><italic>Wolbachia</italic> endosymbionts carried by filarial nematodes give rise to the neglected diseases African river blindness and lymphatic filariasis afflicting millions worldwide. Here we identify new <italic>Wolbachia</italic>-disrupting compounds by conducting high-throughput cell-based chemical screens using a <italic>Wolbachia</italic>-infected, fluorescently labeled <italic>Drosophila</italic> cell line. This screen yielded several <italic>Wolbachia</italic>-disrupting compounds including three that resembled Albendazole, a widely used anthelmintic drug that targets nematode microtubules. Follow-up studies demonstrate that a common Albendazole metabolite, Albendazole sulfone, reduces intracellular <italic>Wolbachia</italic> titer both in <italic>Drosophila melanogaster</italic> and <italic>Brugia malayi</italic>, the nematode responsible for lymphatic filariasis. Significantly, Albendazole sulfone does not disrupt <italic>Drosophila</italic> microtubule organization, suggesting that this compound reduces titer through direct targeting of <italic>Wolbachia</italic>. Accordingly, both DNA staining and FtsZ immunofluorescence demonstrates that Albendazole sulfone treatment induces <italic>Wolbachia</italic> elongation, a phenotype indicative of binary fission defects. This suggests that the efficacy of Albendazole in treating filarial nematode-based diseases is attributable to dual targeting of nematode microtubules and their <italic>Wolbachia</italic> endosymbionts.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Hilgenboecker, K" uniqKey="Hilgenboecker K">K Hilgenboecker</name></author><author><name sortKey="Hammerstein, P" uniqKey="Hammerstein P">P Hammerstein</name></author><author><name sortKey="Schlattmann, P" uniqKey="Schlattmann P">P Schlattmann</name></author><author><name sortKey="Telschow, A" uniqKey="Telschow A">A Telschow</name></author><author><name sortKey="Werren, Jh" uniqKey="Werren J">JH Werren</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Serbus, Lr" uniqKey="Serbus L">LR Serbus</name></author><author><name sortKey="Casper Lindley, C" uniqKey="Casper Lindley C">C Casper-Lindley</name></author><author><name sortKey="Landmann, F" 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Lowe</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hoerauf, A" uniqKey="Hoerauf A">A Hoerauf</name></author><author><name sortKey="Nissen Pahle, K" uniqKey="Nissen Pahle K">K Nissen-Pahle</name></author><author><name sortKey="Schmetz, C" uniqKey="Schmetz C">C Schmetz</name></author><author><name sortKey="Henkle Duhrsen, K" uniqKey="Henkle Duhrsen K">K Henkle-Duhrsen</name></author><author><name sortKey="Blaxter, Ml" uniqKey="Blaxter M">ML Blaxter</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Genchi, C" uniqKey="Genchi C">C Genchi</name></author><author><name sortKey="Sacchi, L" uniqKey="Sacchi L">L Sacchi</name></author><author><name sortKey="Bandi, C" uniqKey="Bandi C">C Bandi</name></author><author><name sortKey="Venco, L" uniqKey="Venco L">L Venco</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhang, Jh" uniqKey="Zhang J">JH Zhang</name></author><author><name sortKey="Chung, Td" uniqKey="Chung T">TD Chung</name></author><author><name sortKey="Oldenburg, Kr" uniqKey="Oldenburg K">KR Oldenburg</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Landmann, F" uniqKey="Landmann F">F Landmann</name></author><author><name sortKey="Foster, Jm" uniqKey="Foster J">JM Foster</name></author><author><name sortKey="Slatko, B" uniqKey="Slatko B">B Slatko</name></author><author><name sortKey="Sullivan, W" uniqKey="Sullivan W">W Sullivan</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>France</li><li>États-Unis</li></country><region><li>Californie</li><li>Île-de-France</li></region><settlement><li>Paris</li></settlement></list><tree><country name="États-Unis"><region name="Californie"><name sortKey="Serbus, Laura R" sort="Serbus, Laura R" uniqKey="Serbus L" first="Laura R." last="Serbus">Laura R. Serbus</name></region><name sortKey="Bray, Walter M" sort="Bray, Walter M" uniqKey="Bray W" first="Walter M." last="Bray">Walter M. Bray</name><name sortKey="Landmann, Frederic" sort="Landmann, Frederic" uniqKey="Landmann F" first="Frederic" last="Landmann">Frederic Landmann</name><name sortKey="Lokey, R Scott" sort="Lokey, R Scott" uniqKey="Lokey R" first="R. Scott" last="Lokey">R. Scott Lokey</name><name sortKey="Ruybal, Jordan" sort="Ruybal, Jordan" uniqKey="Ruybal J" first="Jordan" last="Ruybal">Jordan Ruybal</name><name sortKey="Sullivan, William" sort="Sullivan, William" uniqKey="Sullivan W" first="William" last="Sullivan">William Sullivan</name><name sortKey="White, Pamela M" sort="White, Pamela M" uniqKey="White P" first="Pamela M." last="White">Pamela M. White</name></country><country name="France"><region name="Île-de-France"><name sortKey="Debec, Alain" sort="Debec, Alain" uniqKey="Debec A" first="Alain" last="Debec">Alain Debec</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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