Lathosterol Oxidase (Sterol C-5 Desaturase) Deletion Confers Resistance to Amphotericin B and Sensitivity to Acidic Stress in Leishmania major
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2020 |
| Outros Autores: | , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/43690 |
Resumo: | Department of Biological Sciences. Texas Tech University. Lubbock, Texas, USA. |
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Ning, YuFrankfater, CherylHsu, Fong-FuSoares, Rodrigo Pedro PintoCardoso, Camila AlmeidaNogueira, Paula MonalisaLander, Noelia MarinaDocampo, RobertoZhang, Kai2020-09-29T18:21:52Z2020-09-29T18:21:52Z2020NING, Yu et al. Lathosterol Oxidase (Sterol C-5 Desaturase) Deletion Confers Resistance to Amphotericin B and Sensitivity to Acidic Stress in Leishmania major. mSphere, 5, n. 4, :e00380-20,2379-5042https://www.arca.fiocruz.br/handle/icict/4369010.1128/mSphere.00380-20engAmerican Society for MicrobiologyLathosterol Oxidase (Sterol C-5 Desaturase) Deletion Confers Resistance to Amphotericin B and Sensitivity to Acidic Stress in Leishmania majorA deleção da latosterol oxidase (esterol C-5 dessaturase) confere resistência à anfotericina B e sensibilidade ao estresse ácido em Leishmania majorinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleDepartment of Biological Sciences. Texas Tech University. Lubbock, Texas, USA.Mass Spectrometry Resource. Division of Endocrinology, Diabetes, Metabolism, and Lipid Research. Department of Internal Medicinel Washington University School of Medicinel St. Louis, Missouri, USA.Mass Spectrometry Resource. Division of Endocrinology, Diabetes, Metabolism, and Lipid Research. Department of Internal Medicinel Washington University School of Medicinel St. Louis, Missouri, USA.Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil.Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil.Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil.Center for Tropical and Emerging Global Diseases. University of Georgia. Athens, Georgia, USA./Department of Cellular Biology. University of Georgia.Athens, Georgia, USA.Center for Tropical and Emerging Global Diseases. University of Georgia. Athens, Georgia, USA./DepartmentDepartment of Biological Sciences., Texas Tech University. Lubbock, Texas, USALathosterol oxidase (LSO) catalyzes the formation of the C-5–C-6 doublebond in the synthesis of various types of sterols in mammals, fungi, plants, and pro-tozoa. InLeishmaniaparasites, mutations inLSOor other sterol biosynthetic genesare associated with amphotericin B resistance. To investigate the biological roles ofsterol C-5–C-6 desaturation, we generated anLSO-null mutant line (lso)inLeishma-nia major, the causative agent for cutaneous leishmaniasis.lsoparasites lacked theergostane-based sterols commonly found in wild-typeL. majorand instead accumu-lated equivalent sterol species without the C-5–C-6 double bond. These mutant par-asites were replicative in culture and displayed heightened resistance to amphoteri-cin B. However, they survived poorly after reaching the maximal density and werehighly vulnerable to the membrane-disrupting detergent Triton X-100. In addition,lsomutants showed defects in regulating intracellular pH and were hypersensitiveto acidic conditions. They also had potential alterations in the carbohydrate compo-sition of lipophosphoglycan, a membrane-bound virulence factor inLeishmania. Allthese defects inlsowere corrected upon the restoration of LSO expression. To-gether, these findings suggest that the C-5–C-6 double bond is vital for the struc-ture of the sterol core, and while the loss of LSO can lead to amphotericin B resis-tance, it also makesLeishmaniaparasites vulnerable to biologically relevant stress.Leishmania parasiteLeishmaniasisinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-83082https://www.arca.fiocruz.br/bitstream/icict/43690/1/license.txt9193a7c197bc67acd023525e72a03240MD51ORIGINALLathosterol Oxidase.pdfLathosterol Oxidase.pdfapplication/pdf7295448https://www.arca.fiocruz.br/bitstream/icict/43690/2/Lathosterol%20Oxidase.pdf58977c771982d92fd8a54f5216eb42b1MD52TEXTLathosterol Oxidase.pdf.txtLathosterol Oxidase.pdf.txtExtracted texttext/plain2124https://www.arca.fiocruz.br/bitstream/icict/43690/3/Lathosterol%20Oxidase.pdf.txtf0e510a1548c19fbfabf908e3f38800eMD53icict/436902023-08-25 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| dc.title.pt_BR.fl_str_mv |
Lathosterol Oxidase (Sterol C-5 Desaturase) Deletion Confers Resistance to Amphotericin B and Sensitivity to Acidic Stress in Leishmania major |
| dc.title.alternative.none.fl_str_mv |
A deleção da latosterol oxidase (esterol C-5 dessaturase) confere resistência à anfotericina B e sensibilidade ao estresse ácido em Leishmania major |
| title |
Lathosterol Oxidase (Sterol C-5 Desaturase) Deletion Confers Resistance to Amphotericin B and Sensitivity to Acidic Stress in Leishmania major |
| spellingShingle |
Lathosterol Oxidase (Sterol C-5 Desaturase) Deletion Confers Resistance to Amphotericin B and Sensitivity to Acidic Stress in Leishmania major Ning, Yu Leishmania parasite Leishmaniasis |
| title_short |
Lathosterol Oxidase (Sterol C-5 Desaturase) Deletion Confers Resistance to Amphotericin B and Sensitivity to Acidic Stress in Leishmania major |
| title_full |
Lathosterol Oxidase (Sterol C-5 Desaturase) Deletion Confers Resistance to Amphotericin B and Sensitivity to Acidic Stress in Leishmania major |
| title_fullStr |
Lathosterol Oxidase (Sterol C-5 Desaturase) Deletion Confers Resistance to Amphotericin B and Sensitivity to Acidic Stress in Leishmania major |
| title_full_unstemmed |
Lathosterol Oxidase (Sterol C-5 Desaturase) Deletion Confers Resistance to Amphotericin B and Sensitivity to Acidic Stress in Leishmania major |
| title_sort |
Lathosterol Oxidase (Sterol C-5 Desaturase) Deletion Confers Resistance to Amphotericin B and Sensitivity to Acidic Stress in Leishmania major |
| author |
Ning, Yu |
| author_facet |
Ning, Yu Frankfater, Cheryl Hsu, Fong-Fu Soares, Rodrigo Pedro Pinto Cardoso, Camila Almeida Nogueira, Paula Monalisa Lander, Noelia Marina Docampo, Roberto Zhang, Kai |
| author_role |
author |
| author2 |
Frankfater, Cheryl Hsu, Fong-Fu Soares, Rodrigo Pedro Pinto Cardoso, Camila Almeida Nogueira, Paula Monalisa Lander, Noelia Marina Docampo, Roberto Zhang, Kai |
| author2_role |
author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Ning, Yu Frankfater, Cheryl Hsu, Fong-Fu Soares, Rodrigo Pedro Pinto Cardoso, Camila Almeida Nogueira, Paula Monalisa Lander, Noelia Marina Docampo, Roberto Zhang, Kai |
| dc.subject.en.pt_BR.fl_str_mv |
Leishmania parasite Leishmaniasis |
| topic |
Leishmania parasite Leishmaniasis |
| description |
Department of Biological Sciences. Texas Tech University. Lubbock, Texas, USA. |
| publishDate |
2020 |
| dc.date.accessioned.fl_str_mv |
2020-09-29T18:21:52Z |
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2020-09-29T18:21:52Z |
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2020 |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
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NING, Yu et al. Lathosterol Oxidase (Sterol C-5 Desaturase) Deletion Confers Resistance to Amphotericin B and Sensitivity to Acidic Stress in Leishmania major. mSphere, 5, n. 4, :e00380-20, |
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https://www.arca.fiocruz.br/handle/icict/43690 |
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2379-5042 |
| dc.identifier.doi.none.fl_str_mv |
10.1128/mSphere.00380-20 |
| identifier_str_mv |
NING, Yu et al. Lathosterol Oxidase (Sterol C-5 Desaturase) Deletion Confers Resistance to Amphotericin B and Sensitivity to Acidic Stress in Leishmania major. mSphere, 5, n. 4, :e00380-20, 2379-5042 10.1128/mSphere.00380-20 |
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American Society for Microbiology |
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American Society for Microbiology |
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