P-glycoprotein interfering agents potentiate ivermectin susceptibility in ivermectin sensitive and resistant isolates of Teladorsagia circumcincta and Haemonchus contortus
P-glycoprotein (P-gp) homologues, belonging to the ATP Binding Cassette (ABC) transporter family, are thought to play an important role in the resistance of gastro-intestinal nematode parasites against macrocyclic lactones. The aim of this study was to investigate the influence of various P-gp inter...
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| Veröffentlicht in: | Parasitology 2009-08, Vol.136 (9), p.1081-1088 |
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| creator | BARTLEY, D. J. McALLISTER, H. BARTLEY, Y. DUPUY, J. MÉNEZ, C. ALVINERIE, M. JACKSON, F. LESPINE, A. |
| description | P-glycoprotein (P-gp) homologues, belonging to the ATP Binding Cassette (ABC) transporter family, are thought to play an important role in the resistance of gastro-intestinal nematode parasites against macrocyclic lactones. The aim of this study was to investigate the influence of various P-gp interfering compounds on the efficacy of ivermectin (IVM) in sensitive and resistant nematode isolates. The feeding of IVM resistant and sensitive Teladorsagia circumcincta and Haemonchus contortus first-stage larvae (L1) was assessed using a range of IVM concentrations (0·08–40 nm) with or without P-gp inhibitors: valspodar, verapamil, quercetin, ketoconazole and pluronic P85. The P-gp inhibitors were selected on the basis of their ability to interfere with P-gp transport activity in an epithelial cell line over-expressing murine P-gp. In the presence of P-gp interfering agents, the in vitro susceptibility to IVM of both sensitive and resistant isolates of T. circumcincta and H. contortus was increased. These results show that compounds interfering with P-gp transport activity could enhance IVM efficacy in sensitive isolates, and also restore IVM sensitivity in resistant nematodes. These results support the view that ABC transporters can play an important role in resistance to IVM, at least in the free-living stages of these economically important gastro-intestinal nematodes. |
| doi_str_mv | 10.1017/S0031182009990345 |
| format | Article |
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J. ; McALLISTER, H. ; BARTLEY, Y. ; DUPUY, J. ; MÉNEZ, C. ; ALVINERIE, M. ; JACKSON, F. ; LESPINE, A.</creator><creatorcontrib>BARTLEY, D. J. ; McALLISTER, H. ; BARTLEY, Y. ; DUPUY, J. ; MÉNEZ, C. ; ALVINERIE, M. ; JACKSON, F. ; LESPINE, A.</creatorcontrib><description>P-glycoprotein (P-gp) homologues, belonging to the ATP Binding Cassette (ABC) transporter family, are thought to play an important role in the resistance of gastro-intestinal nematode parasites against macrocyclic lactones. The aim of this study was to investigate the influence of various P-gp interfering compounds on the efficacy of ivermectin (IVM) in sensitive and resistant nematode isolates. The feeding of IVM resistant and sensitive Teladorsagia circumcincta and Haemonchus contortus first-stage larvae (L1) was assessed using a range of IVM concentrations (0·08–40 nm) with or without P-gp inhibitors: valspodar, verapamil, quercetin, ketoconazole and pluronic P85. The P-gp inhibitors were selected on the basis of their ability to interfere with P-gp transport activity in an epithelial cell line over-expressing murine P-gp. In the presence of P-gp interfering agents, the in vitro susceptibility to IVM of both sensitive and resistant isolates of T. circumcincta and H. contortus was increased. These results show that compounds interfering with P-gp transport activity could enhance IVM efficacy in sensitive isolates, and also restore IVM sensitivity in resistant nematodes. These results support the view that ABC transporters can play an important role in resistance to IVM, at least in the free-living stages of these economically important gastro-intestinal nematodes.</description><identifier>ISSN: 0031-1820</identifier><identifier>EISSN: 1469-8161</identifier><identifier>DOI: 10.1017/S0031182009990345</identifier><identifier>PMID: 19549355</identifier><identifier>CODEN: PARAAE</identifier><language>eng</language><publisher>Cambridge, UK: Cambridge University Press</publisher><subject>ABC transporters ; Animals ; anthelmintic resistance ; Anthelmintics - pharmacology ; ATP-Binding Cassette, Sub-Family B, Member 1 - antagonists & inhibitors ; ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism ; Biological and medical sciences ; Biological Transport ; Drug Resistance ; Economic importance ; Fundamental and applied biological sciences. Psychology ; General aspects ; General aspects and techniques. Study of several systematic groups. Models ; Haemonchus contortus ; Invertebrates ; ivermectin ; Ivermectin - pharmacology ; Larva - drug effects ; Larvae ; Life Sciences ; Nematodes ; P-glycoprotein ; Parasites ; Teladorsagia circumcincta ; Trichostrongyloidea - drug effects</subject><ispartof>Parasitology, 2009-08, Vol.136 (9), p.1081-1088</ispartof><rights>Copyright © Cambridge University Press 2009</rights><rights>2009 INIST-CNRS</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c472t-17ef59a247b212bc567b317b564efb4ded226b1e1adca904649e80e2275f1503</citedby><cites>FETCH-LOGICAL-c472t-17ef59a247b212bc567b317b564efb4ded226b1e1adca904649e80e2275f1503</cites><orcidid>0000-0001-5144-1242 ; 0000-0001-8153-8555</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.cambridge.org/core/product/identifier/S0031182009990345/type/journal_article$$EHTML$$P50$$Gcambridge$$H</linktohtml><link.rule.ids>164,230,314,776,780,881,27901,27902,55603</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21752100$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19549355$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.inrae.fr/hal-02662392$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>BARTLEY, D. J.</creatorcontrib><creatorcontrib>McALLISTER, H.</creatorcontrib><creatorcontrib>BARTLEY, Y.</creatorcontrib><creatorcontrib>DUPUY, J.</creatorcontrib><creatorcontrib>MÉNEZ, C.</creatorcontrib><creatorcontrib>ALVINERIE, M.</creatorcontrib><creatorcontrib>JACKSON, F.</creatorcontrib><creatorcontrib>LESPINE, A.</creatorcontrib><title>P-glycoprotein interfering agents potentiate ivermectin susceptibility in ivermectin sensitive and resistant isolates of Teladorsagia circumcincta and Haemonchus contortus</title><title>Parasitology</title><addtitle>Parasitology</addtitle><description>P-glycoprotein (P-gp) homologues, belonging to the ATP Binding Cassette (ABC) transporter family, are thought to play an important role in the resistance of gastro-intestinal nematode parasites against macrocyclic lactones. The aim of this study was to investigate the influence of various P-gp interfering compounds on the efficacy of ivermectin (IVM) in sensitive and resistant nematode isolates. The feeding of IVM resistant and sensitive Teladorsagia circumcincta and Haemonchus contortus first-stage larvae (L1) was assessed using a range of IVM concentrations (0·08–40 nm) with or without P-gp inhibitors: valspodar, verapamil, quercetin, ketoconazole and pluronic P85. The P-gp inhibitors were selected on the basis of their ability to interfere with P-gp transport activity in an epithelial cell line over-expressing murine P-gp. In the presence of P-gp interfering agents, the in vitro susceptibility to IVM of both sensitive and resistant isolates of T. circumcincta and H. contortus was increased. These results show that compounds interfering with P-gp transport activity could enhance IVM efficacy in sensitive isolates, and also restore IVM sensitivity in resistant nematodes. These results support the view that ABC transporters can play an important role in resistance to IVM, at least in the free-living stages of these economically important gastro-intestinal nematodes.</description><subject>ABC transporters</subject><subject>Animals</subject><subject>anthelmintic resistance</subject><subject>Anthelmintics - pharmacology</subject><subject>ATP-Binding Cassette, Sub-Family B, Member 1 - antagonists & inhibitors</subject><subject>ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism</subject><subject>Biological and medical sciences</subject><subject>Biological Transport</subject><subject>Drug Resistance</subject><subject>Economic importance</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>General aspects</subject><subject>General aspects and techniques. Study of several systematic groups. Models</subject><subject>Haemonchus contortus</subject><subject>Invertebrates</subject><subject>ivermectin</subject><subject>Ivermectin - pharmacology</subject><subject>Larva - drug effects</subject><subject>Larvae</subject><subject>Life Sciences</subject><subject>Nematodes</subject><subject>P-glycoprotein</subject><subject>Parasites</subject><subject>Teladorsagia circumcincta</subject><subject>Trichostrongyloidea - drug effects</subject><issn>0031-1820</issn><issn>1469-8161</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kd-K1DAUxoso7rj6AN5IEBS8qCZp_kwvl0VnhAFHnAvvQpqezmZtkzFJF-eZfElTp8yK4kUI5Pudk_OdryieE_yWYCLffcG4ImRJMa7rGleMPygWhIm6XBJBHhaLSS4n_aJ4EuMtxlhUgj4uLkjNWV1xvih-bst9fzT-EHwC65B1CUIHwbo90ntwKaJDVlyyOgGydxAGMCmDcYwGDsk2trfpiKbSP0Rw0ab8gLRrUYBoY9IuIRt9n_tE5Du0g163PkS9txoZG8w4GOtM0r9r1hoG78zNGJHxLvmQxvi0eNTpPsKz-b4sdh_e767X5ebT6uP11aY0TNJUEgkdrzVlsqGENoYL2VRENlww6BrWQkupaAgQ3RpdYyZYDUsMlEreEY6ry-LNqe2N7tUh2EGHo_LaqvXVRk1vmApBq5rekcy-PrF5f99HiEkNNu-l77UDP0YlJFtygVkGX_4F3voxuGxD0RwZloRO3cgJMsHHGKA7f0-wmhJX_ySea17MjcdmgPa-Yo44A69mQEej-y5oZ2w8c5RITgmebJcnLmcFP866Dt-yi0pyJVaf89muVvV2p75mvpqH1UMTbLuHe0v_H_cX6UDVhg</recordid><startdate>20090801</startdate><enddate>20090801</enddate><creator>BARTLEY, D. J.</creator><creator>McALLISTER, H.</creator><creator>BARTLEY, Y.</creator><creator>DUPUY, J.</creator><creator>MÉNEZ, C.</creator><creator>ALVINERIE, M.</creator><creator>JACKSON, F.</creator><creator>LESPINE, A.</creator><general>Cambridge University Press</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TM</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ATCPS</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>RC3</scope><scope>7X8</scope><scope>1XC</scope><orcidid>https://orcid.org/0000-0001-5144-1242</orcidid><orcidid>https://orcid.org/0000-0001-8153-8555</orcidid></search><sort><creationdate>20090801</creationdate><title>P-glycoprotein interfering agents potentiate ivermectin susceptibility in ivermectin sensitive and resistant isolates of Teladorsagia circumcincta and Haemonchus contortus</title><author>BARTLEY, D. J. ; McALLISTER, H. ; BARTLEY, Y. ; DUPUY, J. ; MÉNEZ, C. ; ALVINERIE, M. ; JACKSON, F. ; LESPINE, A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c472t-17ef59a247b212bc567b317b564efb4ded226b1e1adca904649e80e2275f1503</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>ABC transporters</topic><topic>Animals</topic><topic>anthelmintic resistance</topic><topic>Anthelmintics - pharmacology</topic><topic>ATP-Binding Cassette, Sub-Family B, Member 1 - antagonists & inhibitors</topic><topic>ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism</topic><topic>Biological and medical sciences</topic><topic>Biological Transport</topic><topic>Drug Resistance</topic><topic>Economic importance</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>General aspects</topic><topic>General aspects and techniques. Study of several systematic groups. Models</topic><topic>Haemonchus contortus</topic><topic>Invertebrates</topic><topic>ivermectin</topic><topic>Ivermectin - pharmacology</topic><topic>Larva - drug effects</topic><topic>Larvae</topic><topic>Life Sciences</topic><topic>Nematodes</topic><topic>P-glycoprotein</topic><topic>Parasites</topic><topic>Teladorsagia circumcincta</topic><topic>Trichostrongyloidea - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>BARTLEY, D. J.</creatorcontrib><creatorcontrib>McALLISTER, H.</creatorcontrib><creatorcontrib>BARTLEY, Y.</creatorcontrib><creatorcontrib>DUPUY, J.</creatorcontrib><creatorcontrib>MÉNEZ, C.</creatorcontrib><creatorcontrib>ALVINERIE, M.</creatorcontrib><creatorcontrib>JACKSON, F.</creatorcontrib><creatorcontrib>LESPINE, A.</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Agricultural Science Collection</collection><collection>ProQuest Health and Medical</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><jtitle>Parasitology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>BARTLEY, D. J.</au><au>McALLISTER, H.</au><au>BARTLEY, Y.</au><au>DUPUY, J.</au><au>MÉNEZ, C.</au><au>ALVINERIE, M.</au><au>JACKSON, F.</au><au>LESPINE, A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>P-glycoprotein interfering agents potentiate ivermectin susceptibility in ivermectin sensitive and resistant isolates of Teladorsagia circumcincta and Haemonchus contortus</atitle><jtitle>Parasitology</jtitle><addtitle>Parasitology</addtitle><date>2009-08-01</date><risdate>2009</risdate><volume>136</volume><issue>9</issue><spage>1081</spage><epage>1088</epage><pages>1081-1088</pages><issn>0031-1820</issn><eissn>1469-8161</eissn><coden>PARAAE</coden><abstract>P-glycoprotein (P-gp) homologues, belonging to the ATP Binding Cassette (ABC) transporter family, are thought to play an important role in the resistance of gastro-intestinal nematode parasites against macrocyclic lactones. The aim of this study was to investigate the influence of various P-gp interfering compounds on the efficacy of ivermectin (IVM) in sensitive and resistant nematode isolates. The feeding of IVM resistant and sensitive Teladorsagia circumcincta and Haemonchus contortus first-stage larvae (L1) was assessed using a range of IVM concentrations (0·08–40 nm) with or without P-gp inhibitors: valspodar, verapamil, quercetin, ketoconazole and pluronic P85. The P-gp inhibitors were selected on the basis of their ability to interfere with P-gp transport activity in an epithelial cell line over-expressing murine P-gp. In the presence of P-gp interfering agents, the in vitro susceptibility to IVM of both sensitive and resistant isolates of T. circumcincta and H. contortus was increased. These results show that compounds interfering with P-gp transport activity could enhance IVM efficacy in sensitive isolates, and also restore IVM sensitivity in resistant nematodes. These results support the view that ABC transporters can play an important role in resistance to IVM, at least in the free-living stages of these economically important gastro-intestinal nematodes.</abstract><cop>Cambridge, UK</cop><pub>Cambridge University Press</pub><pmid>19549355</pmid><doi>10.1017/S0031182009990345</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0001-5144-1242</orcidid><orcidid>https://orcid.org/0000-0001-8153-8555</orcidid></addata></record> |
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| ispartof | Parasitology, 2009-08, Vol.136 (9), p.1081-1088 |
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| language | eng |
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| subjects | ABC transporters Animals anthelmintic resistance Anthelmintics - pharmacology ATP-Binding Cassette, Sub-Family B, Member 1 - antagonists & inhibitors ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism Biological and medical sciences Biological Transport Drug Resistance Economic importance Fundamental and applied biological sciences. Psychology General aspects General aspects and techniques. Study of several systematic groups. Models Haemonchus contortus Invertebrates ivermectin Ivermectin - pharmacology Larva - drug effects Larvae Life Sciences Nematodes P-glycoprotein Parasites Teladorsagia circumcincta Trichostrongyloidea - drug effects |
| title | P-glycoprotein interfering agents potentiate ivermectin susceptibility in ivermectin sensitive and resistant isolates of Teladorsagia circumcincta and Haemonchus contortus |
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