疟原虫二氢叶酸合成酶的新型 K540N 突变导致磺胺类药物耐药水平低于 K540E 突变。
Novel K540N mutation in Plasmodium falciparum dihydropteroate synthetase confers a lower level of sulfa drug resistance than does a K540E mutation.
机构信息
Department of Biotechnology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India.
出版信息
Antimicrob Agents Chemother. 2011 May;55(5):2481-2. doi: 10.1128/AAC.01394-10. Epub 2011 Feb 22.
Abstract
Sulfadoxine (SDX) and sulfamethoxazole (SMX) each inhibit the Plasmodium falciparum dihydropteroate synthetase (PfDHPS), and certain point mutations in this enzyme yield the drug-resistant parasite. Using a simple Escherichia coli model system, we describe here the effect of the recently reported novel K540N mutation in PfDHPS on the level of SDX/SMX resistance. The survival rate of the transformed E. coli (DHPS-deficient strain) under different SDX or SMX concentrations revealed that the K540N mutation confers a lower level of drug resistance than its contemporary K540E mutation. Further, SMX was more effective than SDX in the E. coli system.
摘要
磺胺多辛（SDX）和磺胺甲恶唑（SMX）均可抑制恶性疟原虫二氢叶酸合成酶（PfDHPS），而该酶的某些点突变可导致寄生虫对药物产生耐药性。本研究利用简单的大肠杆菌模型系统，描述了最近报道的 PfDHPS 中的新型 K540N 突变对 SDX/SMX 耐药水平的影响。在不同 SDX 或 SMX 浓度下，转化的大肠杆菌（DHPS 缺陷株）的存活率表明，K540N 突变比其当代 K540E 突变导致的耐药水平更低。此外，SMX 在大肠杆菌系统中比 SDX 更有效。
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