دورية أكاديمية
أعرض في EDS

A novel ABCG-like transporter of Trypanosoma cruzi is involved in natural resistance to benznidazole.

التفاصيل البيبلوغرافية
العنوان: A novel ABCG-like transporter of Trypanosoma cruzi is involved in natural resistance to benznidazole.
المؤلفون: Zingales B; Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, SP, Brasil., Araujo RG; Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, SP, Brasil., Moreno M; Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, SP, Brasil., Franco J; Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, SP, Brasil., Aguiar PH; Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil., Nunes SL; Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, SP, Brasil., Silva MN; Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, SP, Brasil., Ienne S; Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, SP, Brasil., Machado CR; Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil., Brandão A; Laboratório Interdisciplinar de Pesquisas Médicas, Instituto Oswaldo Cruz-Fiocruz, Rio de Janeiro, RJ, Brasil.
المصدر: Memorias do Instituto Oswaldo Cruz [Mem Inst Oswaldo Cruz] 2015 May; Vol. 110 (3), pp. 433-44. Date of Electronic Publication: 2015 Apr 28.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Instituto Oswaldo Cruz Country of Publication: Brazil NLM ID: 7502619 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1678-8060 (Electronic) Linking ISSN: 00740276 NLM ISO Abbreviation: Mem Inst Oswaldo Cruz Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Rio de Janeiro : Instituto Oswaldo Cruz
مواضيع طبية MeSH: ATP-Binding Cassette Transporters/*genetics , Drug Resistance/*genetics , Nitroimidazoles/*pharmacology , Trypanocidal Agents/*pharmacology , Trypanosoma cruzi/*drug effects , Trypanosoma cruzi/*genetics, Animals ; DNA, Protozoan/genetics ; Genotype ; Humans ; Membrane Transport Proteins/genetics ; Parasitic Sensitivity Tests ; Phylogeny
مستخلص: Benznidazole (BZ) is one of the two drugs used for Chagas disease treatment. Nevertheless therapeutic failures of BZ have been reported, which were mostly attributed to variable drug susceptibility among Trypanosoma cruzi strains. ATP-binding cassette (ABC) transporters are involved in a variety of translocation processes and some members have been implicated in drug resistance. Here we report the characterisation of the first T. cruzi ABCG transporter gene, named TcABCG1, which is over-expressed in parasite strains naturally resistant to BZ. Comparison of TcABCG1 gene sequence of two TcI BZ-resistant strains with CL Brener BZ-susceptible strain showed several single nucleotide polymorphisms, which determined 11 amino acid changes. CL Brener transfected with TcI transporter genes showed 40-47% increased resistance to BZ, whereas no statistical significant increment in drug resistance was observed when CL Brener was transfected with the homologous gene. Only in the parasites transfected with TcI genes there was 2-2.6-fold increased abundance of TcABCG1 transporter protein. The analysis in wild type strains also suggests that the level of TcABCG1 transporter is related to BZ natural resistance. The characteristics of untranslated regions of TcABCG1 genes of BZ-susceptible and resistant strains were investigated by computational tools.
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المشرفين على المادة: 0 (ATP-Binding Cassette Transporters)
0 (DNA, Protozoan)
0 (Membrane Transport Proteins)
0 (Nitroimidazoles)
0 (Trypanocidal Agents)
YC42NRJ1ZD (benzonidazole)
تواريخ الأحداث: Date Created: 20150507 Date Completed: 20160302 Latest Revision: 20181113
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC4489481
DOI: 10.1590/0074-02760140407
PMID: 25946152
قاعدة البيانات: MEDLINE
الوصف
تدمد:1678-8060
DOI:10.1590/0074-02760140407