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Diversity and natural selection of Merozoite surface Protein-1 in three species of human malaria parasites: Contribution from South-East Asian isolates
Molecular and Biochemical Parasitology ( IF 1.5 ) Pub Date : 2021-06-01 , DOI: 10.1016/j.molbiopara.2021.111390
Xiang Ting Goh 1 , Yvonne A L Lim 2 , Ping Chin Lee 3 , Veeranoot Nissapatorn 4 , Kek Heng Chua 1
Affiliation  

The present study aimed to examine the genetic diversity of human malaria parasites (i.e., P. falciparum, P. vivax and P. knowlesi) in Malaysia and southern Thailand targeting the 19-kDa C-terminal region of Merozoite Surface Protein-1 (MSP-119). This region is essential for the recognition and invasion of erythrocytes and it is considered one of the leading candidates for asexual blood stage vaccines. However, the genetic data of MSP-119 among human malaria parasites in Malaysia is limited and there is also a need to update the current sequence diversity of this gene region among the Thailand isolates. In this study, genomic DNA was extracted from 384 microscopy-positive blood samples collected from patients who attended the hospitals or clinics in Malaysia and malaria clinics in Thailand from the year 2008 to 2016. The MSP-119 was amplified using PCR followed by bidirectional sequencing. DNA sequences identified in the present study were subjected to Median-joining network analysis with sequences of MSP-119 obtained from GenBank. DNA sequence analysis revealed that PfMSP-119 of Malaysian and Thailand isolates was not genetically conserved as high number of haplotypes were detected and positive selection was prevalent in PfMSP-119, hence questioning its suitability to be used as a vaccine candidate. A novel haplotype (Q/TNG/L) was also detected in Thailand P. falciparum isolate. In contrast, PvMSP-119 was highly conserved, however for the first time, a non-synonymous substitution (A1657S) was reported among Malaysian isolates. As for PkMSP-119, the presence of purifying selection and low nucleotide diversity indicated that it might be a potential vaccine target for P. knowlesi.



中文翻译:

三种人类疟原虫中裂殖子表面蛋白 1 的多样性和自然选择:来自东南亚分离株的贡献

本研究旨在检测马来西亚和泰国南部人类疟疾寄生虫(即恶性疟原虫间日疟原虫诺氏疟原虫)的遗传多样性,靶向裂殖子表面蛋白 1 ( MSP)的 19-kDa C 末端区域。-1 19)。该区域对于红细胞的识别和入侵至关重要,它被认为是无性血阶段疫苗的主要候选者之一。然而,MSP-1 19的基因数据马来西亚人类疟疾寄生虫中的数量有限,还需要更新泰国分离株中该基因区域的当前序列多样性。在这项研究中,从 2008 年至 2016 年在马来西亚的医院或诊所以及泰国的疟疾诊所就诊的患者收集的 384 份显微镜检查阳性血液样本中提取了基因组 DNA。MSP-1 19使用 PCR 扩增,然后进行双向扩增测序。本研究中鉴定的 DNA 序列使用从 GenBank 获得的MSP-1 19序列进行中值连接网络分析。DNA 序列分析表明PfMSP-1 19马来西亚和泰国分离株的基因不保守,因为检测到大量单倍型,并且在PfMSP-1 19 中普遍存在阳性选择,因此质疑其作为候选疫苗的适用性。在泰国恶性疟原虫分离株中也检测到了一种新的单倍型 (Q/TNG/L) 。相比之下,PvMSP-1 19是高度保守的,但是第一次在马来西亚分离株中报告了非同义替换(A1657S)。至于PkMSP-1 19,纯化选择和低核苷酸多样性的存在表明它可能是诺氏假单胞菌的潜在疫苗靶标

更新日期:2021-06-05
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