ATP binding cassette transporter mediates both heme and pesticide detoxification in tick midgut cells
Autor(a) principal: | |
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Data de Publicação: | 2015 |
Outros Autores: | , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFRGS |
Texto Completo: | http://hdl.handle.net/10183/224429 |
Resumo: | In ticks, the digestion of blood occurs intracellularly and proteolytic digestion of hemoglobin takes place in a dedicated type of lysosome, the digest vesicle, followed by transfer of the heme moiety of hemoglobin to a specialized organelle that accumulates large heme aggregates, called hemosomes. In the present work, we studied the uptake of fluorescent metalloporphyrins, used as heme analogs, and amitraz, one of the most regularly used acaricides to control cattle tick infestations, by Rhipicephalus (Boophilus) microplus midgut cells. Both compounds were taken up by midgut cells in vitro and accumulated inside the hemosomes. Transport of both molecules was sensitive to cyclosporine A (CsA), a wellknown inhibitor of ATP binding cassette (ABC) transporters. Rhodamine 123, a fluorescent probe that is also a recognized ABC substrate, was similarly directed to the hemosome in a CsA-sensitive manner. Using an antibody against conserved domain of PgP-1-type ABC transporter, we were able to immunolocalize PgP-1 in the digest vesicle membranes. Comparison between two R. microplus strains that were resistant and susceptible to amitraz revealed that the resistant strain detoxified both amitraz and Sn-Pp IX more efficiently than the susceptible strain, a process that was also sensitive to CsA. A transcript containing an ABC transporter signature exhibited 2.5-fold increased expression in the amitraz-resistant strain when compared with the susceptible strain. RNAi-induced down-regulation of this ABC transporter led to the accumulation of metalloporphyrin in the digestive vacuole, interrupting heme traffic to the hemosome. This evidence further confirms that this transcript codes for a heme transporter. This is the first report of heme transport in a blood-feeding organism. While the primary physiological function of the hemosome is to detoxify heme and attenuate its toxicity, we suggest that the use of this acaricide detoxification pathway by ticks may represent a new molecular mechanism of resistance to pesticides. |
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Lara, Flávio AlvesPohl, Paula CristianeGandara, Ana CarolineFerreira, Jessica da SilvaNascimento-Silva, Maria ClaraBechara, Gervásio HenriqueSorgine, Marcos Henrique FerreiraAlmeida, Igor Correia deVaz Junior, Itabajara da SilvaOliveira, Pedro Lagerblad de2021-07-23T04:41:34Z20151932-6203http://hdl.handle.net/10183/224429000971802In ticks, the digestion of blood occurs intracellularly and proteolytic digestion of hemoglobin takes place in a dedicated type of lysosome, the digest vesicle, followed by transfer of the heme moiety of hemoglobin to a specialized organelle that accumulates large heme aggregates, called hemosomes. In the present work, we studied the uptake of fluorescent metalloporphyrins, used as heme analogs, and amitraz, one of the most regularly used acaricides to control cattle tick infestations, by Rhipicephalus (Boophilus) microplus midgut cells. Both compounds were taken up by midgut cells in vitro and accumulated inside the hemosomes. Transport of both molecules was sensitive to cyclosporine A (CsA), a wellknown inhibitor of ATP binding cassette (ABC) transporters. Rhodamine 123, a fluorescent probe that is also a recognized ABC substrate, was similarly directed to the hemosome in a CsA-sensitive manner. Using an antibody against conserved domain of PgP-1-type ABC transporter, we were able to immunolocalize PgP-1 in the digest vesicle membranes. Comparison between two R. microplus strains that were resistant and susceptible to amitraz revealed that the resistant strain detoxified both amitraz and Sn-Pp IX more efficiently than the susceptible strain, a process that was also sensitive to CsA. A transcript containing an ABC transporter signature exhibited 2.5-fold increased expression in the amitraz-resistant strain when compared with the susceptible strain. RNAi-induced down-regulation of this ABC transporter led to the accumulation of metalloporphyrin in the digestive vacuole, interrupting heme traffic to the hemosome. This evidence further confirms that this transcript codes for a heme transporter. This is the first report of heme transport in a blood-feeding organism. While the primary physiological function of the hemosome is to detoxify heme and attenuate its toxicity, we suggest that the use of this acaricide detoxification pathway by ticks may represent a new molecular mechanism of resistance to pesticides.application/pdfengPLOS ONE. San Francisco, CA. Vol. 10, no. 8 (Aug. 2015), e0134779, 20 p.EntomologiaBiotecnologiaRhipicephalus microplusResistência à pesticidaATP binding cassette transporter mediates both heme and pesticide detoxification in tick midgut cellsEstrangeiroinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFRGSinstname:Universidade Federal do Rio Grande do Sul (UFRGS)instacron:UFRGSTEXT000971802.pdf.txt000971802.pdf.txtExtracted Texttext/plain72074http://www.lume.ufrgs.br/bitstream/10183/224429/2/000971802.pdf.txtf9753c8851c87e48616acdcc3417f08fMD52ORIGINAL000971802.pdfTexto completo (inglês)application/pdf6748083http://www.lume.ufrgs.br/bitstream/10183/224429/1/000971802.pdf0febe6bad842ab7fb38d1aad3c3aad7eMD5110183/2244292021-08-18 04:50:08.60801oai:www.lume.ufrgs.br:10183/224429Repositório de PublicaçõesPUBhttps://lume.ufrgs.br/oai/requestopendoar:2021-08-18T07:50:08Repositório Institucional da UFRGS - Universidade Federal do Rio Grande do Sul (UFRGS)false |
dc.title.pt_BR.fl_str_mv |
ATP binding cassette transporter mediates both heme and pesticide detoxification in tick midgut cells |
title |
ATP binding cassette transporter mediates both heme and pesticide detoxification in tick midgut cells |
spellingShingle |
ATP binding cassette transporter mediates both heme and pesticide detoxification in tick midgut cells Lara, Flávio Alves Entomologia Biotecnologia Rhipicephalus microplus Resistência à pesticida |
title_short |
ATP binding cassette transporter mediates both heme and pesticide detoxification in tick midgut cells |
title_full |
ATP binding cassette transporter mediates both heme and pesticide detoxification in tick midgut cells |
title_fullStr |
ATP binding cassette transporter mediates both heme and pesticide detoxification in tick midgut cells |
title_full_unstemmed |
ATP binding cassette transporter mediates both heme and pesticide detoxification in tick midgut cells |
title_sort |
ATP binding cassette transporter mediates both heme and pesticide detoxification in tick midgut cells |
author |
Lara, Flávio Alves |
author_facet |
Lara, Flávio Alves Pohl, Paula Cristiane Gandara, Ana Caroline Ferreira, Jessica da Silva Nascimento-Silva, Maria Clara Bechara, Gervásio Henrique Sorgine, Marcos Henrique Ferreira Almeida, Igor Correia de Vaz Junior, Itabajara da Silva Oliveira, Pedro Lagerblad de |
author_role |
author |
author2 |
Pohl, Paula Cristiane Gandara, Ana Caroline Ferreira, Jessica da Silva Nascimento-Silva, Maria Clara Bechara, Gervásio Henrique Sorgine, Marcos Henrique Ferreira Almeida, Igor Correia de Vaz Junior, Itabajara da Silva Oliveira, Pedro Lagerblad de |
author2_role |
author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Lara, Flávio Alves Pohl, Paula Cristiane Gandara, Ana Caroline Ferreira, Jessica da Silva Nascimento-Silva, Maria Clara Bechara, Gervásio Henrique Sorgine, Marcos Henrique Ferreira Almeida, Igor Correia de Vaz Junior, Itabajara da Silva Oliveira, Pedro Lagerblad de |
dc.subject.por.fl_str_mv |
Entomologia Biotecnologia Rhipicephalus microplus Resistência à pesticida |
topic |
Entomologia Biotecnologia Rhipicephalus microplus Resistência à pesticida |
description |
In ticks, the digestion of blood occurs intracellularly and proteolytic digestion of hemoglobin takes place in a dedicated type of lysosome, the digest vesicle, followed by transfer of the heme moiety of hemoglobin to a specialized organelle that accumulates large heme aggregates, called hemosomes. In the present work, we studied the uptake of fluorescent metalloporphyrins, used as heme analogs, and amitraz, one of the most regularly used acaricides to control cattle tick infestations, by Rhipicephalus (Boophilus) microplus midgut cells. Both compounds were taken up by midgut cells in vitro and accumulated inside the hemosomes. Transport of both molecules was sensitive to cyclosporine A (CsA), a wellknown inhibitor of ATP binding cassette (ABC) transporters. Rhodamine 123, a fluorescent probe that is also a recognized ABC substrate, was similarly directed to the hemosome in a CsA-sensitive manner. Using an antibody against conserved domain of PgP-1-type ABC transporter, we were able to immunolocalize PgP-1 in the digest vesicle membranes. Comparison between two R. microplus strains that were resistant and susceptible to amitraz revealed that the resistant strain detoxified both amitraz and Sn-Pp IX more efficiently than the susceptible strain, a process that was also sensitive to CsA. A transcript containing an ABC transporter signature exhibited 2.5-fold increased expression in the amitraz-resistant strain when compared with the susceptible strain. RNAi-induced down-regulation of this ABC transporter led to the accumulation of metalloporphyrin in the digestive vacuole, interrupting heme traffic to the hemosome. This evidence further confirms that this transcript codes for a heme transporter. This is the first report of heme transport in a blood-feeding organism. While the primary physiological function of the hemosome is to detoxify heme and attenuate its toxicity, we suggest that the use of this acaricide detoxification pathway by ticks may represent a new molecular mechanism of resistance to pesticides. |
publishDate |
2015 |
dc.date.issued.fl_str_mv |
2015 |
dc.date.accessioned.fl_str_mv |
2021-07-23T04:41:34Z |
dc.type.driver.fl_str_mv |
Estrangeiro info:eu-repo/semantics/article |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10183/224429 |
dc.identifier.issn.pt_BR.fl_str_mv |
1932-6203 |
dc.identifier.nrb.pt_BR.fl_str_mv |
000971802 |
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1932-6203 000971802 |
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http://hdl.handle.net/10183/224429 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.ispartof.pt_BR.fl_str_mv |
PLOS ONE. San Francisco, CA. Vol. 10, no. 8 (Aug. 2015), e0134779, 20 p. |
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info:eu-repo/semantics/openAccess |
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openAccess |
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