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AutorNing, Yu
AutorFrankfater, Cheryl
AutorHsu, Fong-Fu
AutorSoares, Rodrigo Pedro Pinto
AutorCardoso, Camila Almeida
AutorNogueira, Paula Monalisa
AutorLander, Noelia Marina
AutorDocampo, Roberto
AutorZhang, Kai
Data de acesso2020-09-29T18:21:52Z
Data de disponibilização2020-09-29T18:21:52Z
Data do publicação2020
CitaçãoNING, 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,pt_BR
ISSN2379-5042pt_BR
URIhttps://www.arca.fiocruz.br/handle/icict/43690
Idiomaengpt_BR
EditorAmerican Society for Microbiologypt_BR
Direito Autoralopen accesspt_BR
TítuloLathosterol Oxidase (Sterol C-5 Desaturase) Deletion Confers Resistance to Amphotericin B and Sensitivity to Acidic Stress in Leishmania majorpt_BR
Título alternativoA deleção da latosterol oxidase (esterol C-5 dessaturase) confere resistência à anfotericina B e sensibilidade ao estresse ácido em Leishmania major
Tipo do documentoArticlept_BR
DOI10.1128/mSphere.00380-20
Resumo em InglêsLathosterol 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.pt_BR
AfiliaçãoDepartment of Biological Sciences. Texas Tech University. Lubbock, Texas, USA.pt_BR
AfiliaçãoMass Spectrometry Resource. Division of Endocrinology, Diabetes, Metabolism, and Lipid Research. Department of Internal Medicinel Washington University School of Medicinel St. Louis, Missouri, USA.pt_BR
AfiliaçãoMass Spectrometry Resource. Division of Endocrinology, Diabetes, Metabolism, and Lipid Research. Department of Internal Medicinel Washington University School of Medicinel St. Louis, Missouri, USA.pt_BR
AfiliaçãoFundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil.pt_BR
AfiliaçãoFundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil.pt_BR
AfiliaçãoFundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil.pt_BR
AfiliaçãoCenter for Tropical and Emerging Global Diseases. University of Georgia. Athens, Georgia, USA./Department of Cellular Biology. University of Georgia.Athens, Georgia, USA.pt_BR
AfiliaçãoCenter for Tropical and Emerging Global Diseases. University of Georgia. Athens, Georgia, USA./Departmentpt_BR
AfiliaçãoDepartment of Biological Sciences., Texas Tech University. Lubbock, Texas, USApt_BR
Palavras-chave em inglêsLeishmania parasitept_BR
Palavras-chave em inglêsLeishmaniasispt_BR


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