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恶性疟原虫谷氨酸脱氢酶在印度 8 个疟疾流行州保持遗传保守性:探索疟疾消除的新途径。

Plasmodium falciparum glutamate dehydrogenase is genetically conserved across eight malaria endemic states of India: Exploring new avenues of malaria elimination.

机构信息

ICMR-National Institute of Research in Tribal Health (NIRTH), Garha, Jabalpur, India.

Department of P. G. Studies and Research in Biological Science, Rani Durgavati University, Pachpedi, Jabalpur, Madhya Pradesh, India.

出版信息

PLoS One. 2019 Jun 14;14(6):e0218210. doi: 10.1371/journal.pone.0218210. eCollection 2019.

DOI:10.1371/journal.pone.0218210
PMID:31199842
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6568416/
Abstract

Accurate and timely diagnosis is very critical for management, control and elimination of the malaria. Malaria rapid diagnostic tests (RDTs) have improved the diagnosis and management of malaria in remote areas, community and places where microscopy is not available for diagnosis. According to WHO report 2018, Plasmodium falciparum malaria constitutes more than 50% of malaria cases in India. Most of the RDTs used for diagnosis of falciparum malaria today employ HRP2 as a target antigen. However, low density parasitemia and deletion of hrp-2 gene in P. falciparum leads to false negative results and necessitates the development of alternative/ new or improved RDT for malaria diagnosis. We have analysed the genetic diversity and homology modelling of Pfgdh (glutamate dehydrogenase), ldh (lactate dehydrogenase) and aldolase genes in P. falciparum isolates from the eight endemic states of India to assess their potential as antigen for RDT development. We observed negligible sequence diversity in Pfgdh in comparison to the low level of diversity in ldh and aldolase gene. No structural or functional changes were observed in modelling studies and all three genes were under negative purifying selection pressure. The highly conserved nature of pfgdh gene suggests that GDH could be a potential target molecule for Pan/Pf diagnostic test for malaria.

摘要

准确及时的诊断对于疟疾的管理、控制和消除至关重要。疟疾快速诊断检测(RDT)提高了偏远地区、社区和无法进行显微镜诊断的地方的疟疾诊断和管理水平。根据世界卫生组织 2018 年的报告,在印度,恶性疟原虫疟疾构成了 50%以上的疟疾病例。目前用于诊断恶性疟原虫疟疾的大多数 RDT 都以 HRP2 作为靶抗原。然而,低密度寄生虫血症和恶性疟原虫中 hrp-2 基因的缺失导致假阴性结果,因此需要开发替代/新的或改进的 RDT 来进行疟疾诊断。我们分析了来自印度 8 个流行地区的恶性疟原虫分离株的 Pfgdh(谷氨酸脱氢酶)、ldh(乳酸脱氢酶)和 aldolase 基因的遗传多样性和同源建模,以评估它们作为 RDT 开发抗原的潜力。与 ldh 和 aldolase 基因的低度多样性相比,我们观察到 Pfgdh 基因的序列多样性可忽略不计。建模研究中未观察到结构或功能变化,所有三个基因都受到负净化选择压力。pfgdh 基因的高度保守性表明,GDH 可能是疟疾泛/恶性疟诊断检测的潜在靶分子。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a817/6568416/3e06993bf99b/pone.0218210.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a817/6568416/59c7926398f2/pone.0218210.g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a817/6568416/4dabdc01f80a/pone.0218210.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a817/6568416/c787a79b6802/pone.0218210.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a817/6568416/3e06993bf99b/pone.0218210.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a817/6568416/59c7926398f2/pone.0218210.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a817/6568416/5b8222e992c4/pone.0218210.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a817/6568416/4dabdc01f80a/pone.0218210.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a817/6568416/c787a79b6802/pone.0218210.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a817/6568416/3e06993bf99b/pone.0218210.g005.jpg

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