Mutations in Plasmodium falciparum K13 propeller gene from Bangladesh (2009-2013).
Mutations in Plasmodium falciparum K13 propeller gene from Bangladesh (2009-2013).
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DOI：
10.1186/1475-2875-13-431
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发表时间：
2014-11-18
期刊：
影响因子：
3
通讯作者：
Pillai DR
中科院分区：
文献类型：
--
作者：
Mohon AN;Alam MS;Bayih AG;Folefoc A;Shahinas D;Haque R;Pillai DR
孟加拉国是一个疟疾低流行国家，与印度和缅甸接壤。青蒿素联合疗法(ACT)在孟加拉国仍然很成功。泰国-柬埔寨和泰国-缅甸边境对青蒿素具有抗药性的疟疾寄生虫的增加令人担忧。K13螺旋体基因(PF3D7_1343700或PF130238)突变与体外青蒿素耐药性和体内寄生虫清除缓慢有关。该小组着手评估在柬埔寨看到的突变是否出现在孟加拉国，在那里，ACT的使用现在是十年来的标准。样本取自2009至2013年间孟加拉国7个流行区Upazila卫生院(UHC)感染恶性疟原虫的患者。这些地区包括Khagrachari(Matiranga UHC)、Rangamati(Rajparali UHC)、Cox‘s Bazar(Ramu和UkhiaUHC)、Bandarban(Lama UHC)、Mymensingh(Haluaghat UHC)、Netrokona(Durapur和Kalmakanda UHC)和Moulvibazar(Sreemangal和Kamalganj UHC)。在296份镜检阳性的恶性疟原虫标本中，271份(91.6%)同时经实时荧光定量和套式聚合酶链式反应证实为单感染。对253份(93.4%)样品的K13螺旋桨基因进行了双向测序。在孟加拉临床分离株中发现1个非同义突变(A578S)。A578S突变被确认，并位于C580Y突变附近，C580Y突变是导致柬埔寨寄生虫清除延迟的主要突变。基于计算模型，A578S应该对蛋白质的三级结构有显着的影响。这些数据表明，孟加拉国的恶性疟原虫仍然没有与寄生虫清除延迟有关的C580Y突变。然而，突变A578S是存在的，基于结构分析可能会影响K13基因的功能。还需要进一步的体内临床研究来验证这种突变的效果。
Bangladesh is a malaria hypo-endemic country sharing borders with India and Myanmar. Artemisinin combination therapy (ACT) remains successful in Bangladesh. An increase of artemisinin-resistant malaria parasites on the Thai-Cambodia and Thai-Myanmar borders is worrisome. K13 propeller gene (PF3D7_1343700 or PF13_0238) mutations have been linked to both in vitro artemisinin resistance and in vivo slow parasite clearance rates. This group undertook to evaluate if mutations seen in Cambodia have emerged in Bangladesh where ACT use is now standard for a decade. Samples were obtained from Plasmodium falciparum-infected malaria patients from Upazila health complexes (UHC) between 2009 and 2013 in seven endemic districts of Bangladesh. These districts included Khagrachari (Matiranga UHC), Rangamati (Rajasthali UHC), Cox’s Bazar (Ramu and Ukhia UHC), Bandarban (Lama UHC), Mymensingh (Haluaghat UHC), Netrokona (Durgapur and Kalmakanda UHC), and Moulvibazar (Sreemangal and Kamalganj UHC). Out of 296 microscopically positive P. falciparum samples, 271 (91.6%) were confirmed as mono-infections by both real-time PCR and nested PCR. The K13 propeller gene from 253 (93.4%) samples was sequenced bi-directionally. One non-synonymous mutation (A578S) was found in Bangladeshi clinical isolates. The A578S mutation was confirmed and lies adjacent to the C580Y mutation, the major mutation causing delayed parasite clearance in Cambodia. Based on computational modeling A578S should have a significant effect on tertiary structure of the protein. The data suggest that P. falciparum in Bangladesh remains free of the C580Y mutation linked to delayed parasite clearance. However, the mutation A578S is present and based on structural analysis could affect K13 gene function. Further in vivo clinical studies are required to validate the effect of this mutation.
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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影响因子：
56.3
作者：
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Menard, Didier
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3
作者：
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White LJ
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3
作者：
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Haque R