สืบค้นงานวิจัย
Use of bacterial surrogates as a tool to explore antimalarial drug interaction: Synergism between inhibitors of malarial dihydrofolate reductase and dihydropteroate synthase
Talawanich Y. - ไม่ระบุหน่วยงาน
ชื่อเรื่อง (EN): Use of bacterial surrogates as a tool to explore antimalarial drug interaction: Synergism between inhibitors of malarial dihydrofolate reductase and dihydropteroate synthase
ผู้แต่ง / หัวหน้าโครงการ (EN): Talawanich Y.
บทคัดย่อ (EN): Interaction between antimalarial drugs is important in determining the outcome of chemotherapy using drug combinations. Inhibitors of dihydrofolate reductase (DHFR) such as pyrimethamine and of dihydropteroate synthase (DHPS) such as sulfa drugs are known to have synergistic interactions. However, studies of the synergism are complicated by the fact that the malaria parasite can also salvage exogenous folates, and the salvage may also be affected by the drugs. It is desirable to have a convenient system to study interaction of DHFR and DHPS inhibitors without such complications. Here, we describe the use of Escherichia coli transformed with malarial DHFR and DHPS, while its own corresponding genes have been inactivated by optimal concentration of trimethoprim and genetic knockout, respectively, to study the interaction of the inhibitors. Marked synergistic effects are observed for all combinations of pyrimethamine and sulfa inhibitors in the presence of trimethoprim. At 0.05. μM trimethoprim, sum of fractional inhibitory concentrations, σFIC of pyrimethamine with sulfadoxine, pyrimethamine with sulfathiazole, pyrimethamine with sulfamethoxazole, and pyrimethamine with dapsone are in the range of 0.24-0.41. These results show synergism between inhibitors of the two enzymes even in the absence of folate transport and uptake. This bacterial surrogate system should be useful as a tool for assessing the interactions of drug combinations between the DHFR and DHPS inhibitors. © 2015 Elsevier B.V.
บทคัดย่อ: ไม่พบข้อมูลจากหน่วยงานต้นทาง
ภาษา (EN): en
เอกสารแนบ (EN): https://www.scopus.com/inward/record.uri?eid=2-s2.0-84930643108&doi=10.1016%2fj.actatropica.2015.05.011&partnerID=40&md5=387d59d81150642d9ca530e531466ca1
เผยแพร่โดย (EN): มหาวิทยาลัยมหิดล
คำสำคัญ (EN): Tetrahydrofolate Dehydrogenase
เจ้าของลิขสิทธิ์ (EN): มหาวิทยาลัยมหิดล
หากไม่พบเอกสารฉบับเต็ม (Full Text) โปรดติดต่อหน่วยงานเจ้าของข้อมูล

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Talawanich Y.. "Use of bacterial surrogates as a tool to explore antimalarial drug interaction: Synergism between inhibitors of malarial dihydrofolate reductase and dihydropteroate synthase". ไม่ระบุหน่วยงาน. ม.ป.ป.

Talawanich Y.. "Use of bacterial surrogates as a tool to explore antimalarial drug interaction: Synergism between inhibitors of malarial dihydrofolate reductase and dihydropteroate synthase". ไม่ระบุหน่วยงาน. ม.ป.ป.. Print.



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Use of bacterial surrogates as a tool to explore antimalarial drug interaction: Synergism between inhibitors of malarial dihydrofolate reductase and dihydropteroate synthase
Talawanich Y.
มหาวิทยาลัยมหิดล
ไม่ระบุวันที่เผยแพร่
Molecular assays for antimalarial drug resistance surveillance: A target product profile Prevalence of Plasmodium falciparum molecular markers of antimalarial drug resistance in a residual malaria focus area in Sabah, Malaysia Dihydrofolate-reductase mutations in plasmodium knowlesi appear unrelated to selective drug pressure from putative human-to-human transmission in Sabah, Malaysia Genetic Variability of Plasmodium malariae dihydropteroate synthase (dhps) in four Asian countries Use of dried blood spot specimens for in-house HIV drug resistance genotyping assay among infants in Thailand Bacterial Diversity and Phylogenetic Analysis of Type II Polyketide Synthase Gene from Manao-Pee Cave, Thailand Whole-genome sequencing analysis of serially isolated multi-drug and extensively drug resistant Mycobacterium tuberculosis from Thai patients Origin of robustness in generating drug-resistant malaria parasites P-glycoprotein transporter in drug development Chloroquine is grossly under dosed in young children with malaria: Implications for drug resistance
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