The implication of dihydrofolate reductase and dihydropteroate synthetase gene mutations in modification of Plasmodium falciparum characteristics.
The implication of dihydrofolate reductase and dihydropteroate synthetase gene mutations in modification of Plasmodium falciparum characteristics.
复制标题
DOI：
10.1186/1475-2875-6-108
复制
发表时间：
2007-08-08
期刊：
影响因子：
3
通讯作者：
Giha HA
中科院分区：
文献类型：
--
作者：
A-Elbasit IE;Alifrangis M;Khalil IF;Bygbjerg IC;Masuadi EM;Elbashir MI;Giha HA
恶性疟原虫二氢叶酸还原酶（DHFR）和二氢蝶酸合成酶（DHPS）是寄生虫代谢中的重要酶。已知dhfr和dhps基因突变与磺胺嘧啶/乙胺嘧啶（SP）抗性相关。研究dhfr/dhps突变对除SP抗性外的寄生虫特性的影响。从153苏丹患者获得的寄生虫感染与SP或SP +氯喹治疗的无并发症恶性疟疾，成功地在9个密码子的dhfr/dhps基因的PCR-ELISA基因型。在dhfr中检测到N51 I、S108 N和C59 R的突变，在dhps中检测到A/S436 F、A437 G、K540 E和A581 G的突变，每次感染的最大突变数为5。根据每次感染的突变密码子数量（突变复数，functional），将感染分为6个等级：野生型（0级;频率，0.03）和functional等级为1至5的感染，累积频率分别为0.97、0.931、0.866、0.719、0.121。有没有显着的关联之间的ESTA和SP反应。重要的是，使用年龄作为替代标记的免疫力对清除具有多种dhfr/dhps突变的寄生虫做出了显着贡献。然而，这些突变具有生存优势，因为它们与配子体发生增加相关。上述dhfr/dhps突变的意义与dhfr 2至dhps 5相关，与基因/密码子位点无关。
The Plasmodium falciparum dihydrofolate reductase (DHFR) and dihydropteroate synthetase (DHPS) are enzymes of central importance in parasite metabolism. The dhfr and dhps gene mutations are known to be associated with sulphadoxine/pyrimethamine (SP) resistance. To investigate the effects of dhfr/dhps mutations on parasite characteristics other than SP resistance. Parasite infections obtained from 153 Sudanese patients with uncomplicated falciparum malaria treated with SP or SP + chloroquine, were successfully genotyped at nine codons in the dhfr/dhps genes by PCR-ELISA. Mutations were detected in dhfr at N51I, S108N and C59R, and in at dhps at A/S436F, A437G, K540E and A581G, the maximum number of mutations per infection were five. Based on number of mutant codons per infection (multiplicity of mutation, MOM), the infections were organized into six grades: wild-types (grade 0; frequency, 0.03) and infections with MOM grades of 1 to 5, with the following cumulative frequency; 0.97, 0.931, 0.866, 0.719, 0.121, respectively. There was no significant association between the MOM and SP response. Importantly, immunity, using age as a surrogate marker, contributed significantly to the clearance of parasites with multiple dhfr/dhps mutations. However, these mutations have a survival advantage as they were associated with increased gametocytogenesis. The above implications of dhfr/dhps mutations were associated with MOM 2 to 5, regardless of the gene/codon locus.
登录
查看更多内容
影响因子：
3.3
作者：
Mockenhaupt, FP;Bousema, JT;Bienzle, U
通讯作者：
Bienzle, U
DOI：
10.4269/ajtmh.2005.72.155
发表时间：
2005-02-01
影响因子：
3.3
作者：
Alifrangis, M;Enosse, S;Bygjerg, IBC
通讯作者：
Bygjerg, IBC
DOI：
10.4269/ajtmh.2003.69.558
发表时间：
2003-11-01
影响因子：
3.3
作者：
Djimdé, AA;Doumbo, OK;Plowe, CV
通讯作者：
Plowe, CV
DOI：
10.1073/pnas.94.25.13944
发表时间：
1997-12-09
影响因子：
11.1
作者：
Triglia, T;Menting, JGT;Cowman, AF
通讯作者：
Cowman, AF
影响因子：
2.9
作者：
Le Bras, J;Durand, R
通讯作者：
Durand, R