Trypanosoma brucei gambiense adaptation to different mammalian sera is associated with VSG expression site plasticity.
Trypanosoma brucei gambiense adaptation to different mammalian sera is associated with VSG expression site plasticity.
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Brucei gambiense对不同哺乳动物血清的适应性锥虫与VSG表达位点可塑性有关。
DOI：
10.1371/journal.pone.0085072
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Bart JM
中科院分区：
文献类型：
--
作者：
Cordon-Obras C;Cano J;González-Pacanowska D;Benito A;Navarro M;Bart JM
布氏冈比亚锥虫感染被广泛认为是一种人类寄生虫病，尽管它也在野生动物和家畜中发现。因此，动物群可以作为水库，限制消除寄生虫在低地方病疫源地。为了更好地理解T. B.为了在当地动物群中发现冈比亚疟原虫，并研究适应的分子机制，我们通过在不同哺乳动物血清中体外培养寄生虫来产生适应细胞系（adapted cells lines，ADCs）。使用针对变异表面糖蛋白（VSG）的特异性抗体，我们发现血清中的VSG在猪、山羊或人血清中维持时表现出不同的VSG变体。尽管新检测到的VSG与所用血清无关，但不同VSG的一致出现表明端粒表达位点（VSG-ES）的共转录基因重塑。因此，分析表达位点相关基因（ESAG）序列以研究可能的多态性选择。ESAG 6和7基因型，编码转铁蛋白受体（TfR），在不同的大肠杆菌中表达的特点。此外，我们定量ESAG 6/7 mRNA水平并分析转铁蛋白（Tf）摄取。有趣的是，最好的生长发生在猪和人血清中，其始终表现出优势的ESAG 7基因型和比小牛和山羊血清中获得的更高的Tf摄取。我们还发现了一个明显的选择特定的ESAG 3基因型在猪和人血清中的ESAG，这表明其他ESAG可能参与宿主适应过程。总而言之，这些结果表明，VSG-ES重塑允许寄生虫表达一组特定的ESAG，以提供在不同宿主中的选择性优势的模型。最后，猪血清寄生虫显示表型适应参数密切相关的人血清寄生虫，但不同的小牛和山羊血清中生长的寄生虫。这些结果表明，猪更适合保持T。B.冈比亚感染支持以前的流行病学结果。
Trypanosoma brucei gambiense infection is widely considered an anthroponosis, although it has also been found in wild and domestic animals. Thus, fauna could act as reservoir, constraining the elimination of the parasite in hypo-endemic foci. To better understand the possible maintenance of T. b. gambiense in local fauna and investigate the molecular mechanisms underlying adaptation, we generated adapted cells lines (ACLs) by in vitro culture of the parasites in different mammalian sera. Using specific antibodies against the Variant Surface Glycoproteins (VSGs) we found that serum ACLs exhibited different VSG variants when maintained in pig, goat or human sera. Although newly detected VSGs were independent of the sera used, the consistent appearance of different VSGs suggested remodelling of the co-transcribed genes at the telomeric Expression Site (VSG-ES). Thus, Expression Site Associated Genes (ESAGs) sequences were analysed to investigate possible polymorphism selection. ESAGs 6 and 7 genotypes, encoding the transferrin receptor (TfR), expressed in different ACLs were characterised. In addition, we quantified the ESAG6/7 mRNA levels and analysed transferrin (Tf) uptake. Interestingly, the best growth occurred in pig and human serum ACLs, which consistently exhibited a predominant ESAG7 genotype and higher Tf uptake than those obtained in calf and goat sera. We also detected an apparent selection of specific ESAG3 genotypes in the pig and human serum ACLs, suggesting that other ESAGs could be involved in the host adaptation processes. Altogether, these results suggest a model whereby VSG-ES remodelling allows the parasite to express a specific set of ESAGs to provide selective advantages in different hosts. Finally, pig serum ACLs display phenotypic adaptation parameters closely related to human serum ACLs but distinct to parasites grown in calf and goat sera. These results suggest a better suitability of swine to maintain T. b. gambiense infection supporting previous epidemiological results.
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DOI：
10.1016/0169-4758(86)90011-6
发表时间：
1986-01-01
期刊：
Parasitology Today
影响因子：
--
作者：
GIBSON W C
通讯作者：
GIBSON W C
DOI：
10.4269/ajtmh.1987.36.533
发表时间：
1987-05-01
影响因子：
3.3
作者：
DIFFLEY, P;SCOTT, JO;TSEN, TNR
通讯作者：
TSEN, TNR
影响因子：
64.8
作者：
Bitter, W;Gerrits, H;Borst, P
通讯作者：
Borst, P
影响因子：
3.6
作者：
Castillo-Acosta, Victor M.;Vidal, Antonio E.;Gonzalez-Pacanowska, Dolores
通讯作者：
Gonzalez-Pacanowska, Dolores
影响因子：
1.5
作者：
DEGREEF, C;IMBERECHTS, H;HAMERS, R
通讯作者：
HAMERS, R