Highly Variable Expression of Merozoite Surface Protein MSPDBL2 in Diverse Plasmodium falciparum Clinical Isolates and Transcriptome Scans for Correlating Genes.
Highly Variable Expression of Merozoite Surface Protein MSPDBL2 in Diverse Plasmodium falciparum Clinical Isolates and Transcriptome Scans for Correlating Genes.
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DOI：
10.1128/mbio.01948-22
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发表时间：
2022-08-30
期刊：
影响因子：
6.4
通讯作者：
Conway DJ
中科院分区：
文献类型：
--
作者：
Hocking SE;Stewart LB;Freville A;Reid AJ;Tarr SJ;Tetteh KKA;Flueck C;Ahouidi AD;Amambua-Ngwa A;Diakite M;Awandare GA;Conway DJ
恶性疟原虫裂殖子表面蛋白MSPDBL2处于强平衡选择状态，是天然获得性抗体的靶点。值得注意的是，MSPDBL2只在任何培养的寄生虫系的少数成熟裂殖体中表达，并且mspdbl2基因的转录随着配子体发育诱导物GDV1的过度表达而增加，因此了解其自然表达是重要的。在这里，通过免疫荧光显微镜和针对MSPDBL2蛋白保守区的抗体，在第一个体外培养周期中分析了成熟裂殖体中的MSPDBL2，这些分离物来自不同西非国家不同感染流行程度的4个人群的96株临床分离株。在大多数菌株中，只有不到1%的成熟裂殖体呈MSPDBL2阳性，但频率分布高度倾斜，9个裂殖体呈3%以上的阳性，1个裂殖体呈73%的阳性。为了研究其他基因座的表达是否与MSPDBL2的表达相关，对17个裂殖体阳性的分离物进行了全转录组测序。在裂殖体中，特定基因的转录本与MSPDBL2阳性以及mspdbl2基因转录本水平呈高度显著的正相关，显示出先前涉及配子发生的基因的过度表达，但不包括配子发生主控调控因子ap2-g。对实验室适应的克隆进行的单细胞转录组分析表明，大多数表达mspdbl2的个体寄生虫不表达ap2-g，这与MSPDBL2标志着一个发育亚群是不同的，但可能与性承诺共存。
The merozoite surface protein MSPDBL2 of Plasmodium falciparum is under strong balancing selection and is a target of naturally acquired antibodies. Remarkably, MSPDBL2 is expressed in only a minority of mature schizonts of any cultured parasite line, and mspdbl2 gene transcription increases in response to overexpression of the gametocyte development inducer GDV1, so it is important to understand its natural expression. Here, MSPDBL2 in mature schizonts was analyzed in the first ex vivo culture cycle of 96 clinical isolates from 4 populations with various levels of infection endemicity in different West African countries, by immunofluorescence microscopy with antibodies against a conserved region of the protein. In most isolates, less than 1% of mature schizonts were positive for MSPDBL2, but the frequency distribution was highly skewed, as nine isolates had more than 3% schizonts positive and one had 73% positive. To investigate whether the expression of other gene loci correlated with MSPDBL2 expression, whole-transcriptome sequencing was performed on schizont-enriched material from 17 of the isolates with a wide range of proportions of schizonts positive. Transcripts of particular genes were highly significantly positively correlated with MSPDBL2 positivity in schizonts as well as with mspdbl2 gene transcript levels, showing overrepresentation of genes implicated previously as involved in gametocytogenesis but not including the gametocytogenesis master regulator ap2-g. Single-cell transcriptome analysis of a laboratory-adapted clone showed that most individual parasites expressing mspdbl2 did not express ap2-g, consistent with MSPDBL2 marking a developmental subpopulation that is distinct but likely to co-occur alongside sexual commitment.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
10.7
作者：
Mobegi VA;Duffy CW;Amambua-Ngwa A;Loua KM;Laman E;Nwakanma DC;MacInnis B;Aspeling-Jones H;Murray L;Clark TG;Kwiatkowski DP;Conway DJ
通讯作者：
Conway DJ
影响因子：
4.4
作者：
Broadbent KM;Broadbent JC;Ribacke U;Wirth D;Rinn JL;Sabeti PC
通讯作者：
Sabeti PC
影响因子：
3.1
作者：
Bowyer, Paul W.;Stewart, Lindsay B.;Conway, David J.
通讯作者：
Conway, David J.
影响因子：
13.6
作者：
Llora-Batlle, Oriol;Michel-Todo, Lucas;Cortes, Alfred
通讯作者：
Cortes, Alfred