Point mutations in the dihydrofolate reductase and dihydropteroate synthetase genes and in vitro susceptibility to pyrimethamine and cycloguanil of Plasmodium falciparum isolates from Papua New Guinea
Point mutations in the dihydrofolate reductase and dihydropteroate synthetase genes and in vitro susceptibility to pyrimethamine and cycloguanil of Plasmodium falciparum isolates from Papua New Guinea
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DOI：
10.4269/ajtmh.1996.55.209
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发表时间：
1996-08-01
影响因子：
3.3
通讯作者：
Cowman, AF
中科院分区：
文献类型：
--
作者：
Reeder, JC;Rieckmann, KH;Cowman, AF
对来自24名巴布亚新几内亚有症状疟疾患者的恶性疟原虫分离株进行了乙胺嘧啶和环胍的敏感性检测。13株菌株对两种药物均敏感，其余菌株表现出不同程度的耐药性。没有发现菌株对一种药物有耐药性，但对乙醚敏感，正相关表明发现了交叉耐药性。从患者染色的血玻片中提取的寄生虫DNA进行扩增和测序，以检测与抗叶酸耐药性相关的二氢叶酸还原酶（DHFR）和二氢叶酸合成酶基因（DHPS）的点突变。所有耐药菌株在DHFR基因密码子108处都有突变，大多数从Ser变为Asn，但有一株从Ser变为Thr，这一变化此前未在野外分离株中报道。DHFR基因Cys-59对Arg的第二次突变出现在具有较高耐药性的分离株中，但并非完全如此。对DHPS基因进行测序，作为磺胺多辛耐药性的预测因子，只显示了一个与敏感分离株DHPS等位基因不同的例子。
Plasmodium falciparum isolates from 24 Papua New Guinean patients with symptomatic malaria were tested for susceptibility to pyrimethamine and cycloguanil. Thirteen isolates were sensitive to both agents and the remainder exhibited varying degrees of resistance. No isolates were found to be resistant to one agent yet sensitive to the ether and a positive correlation suggesting cross-resistance was found. Parasite DNA extracted from the patients' stained blood slides was amplified and sequenced to examine point mutations in the dihydrofolate reductase (DHFR) and dihydropteroate synthetase genes (DHPS) associated with antifolate resistance. All resistant isolates possessed mutations in the DHFR gene at codon 108, the majority changing from Ser to Asn, but one isolate from Ser to Thr, a change not previously reported in field isolates. A second mutation of the DHFR gene at Cys-59 to Arg was present in isolates with higher level resistance, but not exclusively so. Sequencing the DHPS gene, as a predictor of sulfadoxine resistance, revealed only one example that was different from DHPS alleles of sensitive isolates.