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布氏锥虫参考菌株TREU927/4含有罗德西亚布氏锥虫特异性SRA序列,但表现出对人血清相对抗性的独特表型。

The Trypanosoma brucei reference strain TREU927/4 contains T. brucei rhodesiense-specific SRA sequences, but displays a distinct phenotype of relative resistance to human serum.

作者信息

Vanhamme Luc, Renauld Hubert, Lecordier Laurence, Poelvoorde Philippe, Van Den Abbeele Jan, Pays Etienne

机构信息

Laboratory of Molecular Parasitology, Department of Molecular Biology, IBMM, Free University of Brussels, 12, rue des Professeurs Jeener et Brachet, B-6041 Gosselies, Belgium.

出版信息

Mol Biochem Parasitol. 2004 May;135(1):39-47. doi: 10.1016/j.molbiopara.2004.01.004.

Abstract

The Trypanosoma brucei reference strain TREU927/4 exhibits some resistance to lysis by normal human serum (NHS), but this resistance is never complete even after selection. The genome of this strain contains a minimum of eight sequences related to the T. brucei rhodesiense-specific serum resistance-associated gene (SRA), which encodes a truncated variant surface glycoprotein (VSG) conferring full resistance to lysis by NHS. We selected two sequences showing the highest similarity to SRA and also preceded by a region ("cotransposed region") present immediately upstream from SRA in the VSG expression site termed R-ES, where SRA is expressed in T. brucei rhodesiense. Whereas one of these sequences appears to be a pseudogene, the other, which is contained within a cluster of VSG basic copies (BCs), encodes a VSG truncated in the C-terminal domain. In the latter gene, an inserted region encoding surface-exposed loops similar to those of the BoTat 1.20 VSG interrupts the full SRA sequence. Therefore, this gene was termed SRA-BC, for the putative VSG basic copy from which SRA was derived. Neither this gene nor other SRA-like sequences appeared to be responsible for the relative resistance of TREU927/4 to NHS, since (i) transfection of SRA-BC in T. brucei brucei did not confer increased resistance; (ii) SRA transcripts could not be detected in this strain, even when focusing the search on the limited SRA sequence necessary to confer resistance and when using strain-specific SRA probes on RNA from cells selected in the presence of NHS.

摘要

布氏锥虫参考菌株TREU927/4对正常人血清(NHS)介导的裂解表现出一定抗性,但即使经过筛选,这种抗性也从未完全消失。该菌株的基因组至少包含8个与布氏罗得西亚锥虫特异性血清抗性相关基因(SRA)相关的序列,SRA编码一种截短的变异表面糖蛋白(VSG),可赋予对NHS介导裂解的完全抗性。我们选择了两个与SRA相似度最高的序列,且这两个序列之前还有一个区域(“共转座区域”),该区域位于VSG表达位点R-ES中SRA紧上游,而在布氏罗得西亚锥虫中SRA正是在该位点表达。其中一个序列似乎是假基因,另一个包含在VSG基本拷贝(BC)簇中,编码一个C末端结构域截短的VSG。在后一个基因中,一个编码类似于BoTat 1.20 VSG表面暴露环的插入区域中断了完整的SRA序列。因此,该基因被命名为SRA-BC,即推测SRA所源自的VSG基本拷贝。该基因以及其他SRA样序列似乎都与TREU927/4对NHS的相对抗性无关,原因如下:(i)在布氏布氏锥虫中转染SRA-BC并未增强抗性;(ii)即使将搜索重点放在赋予抗性所需的有限SRA序列上,并且在存在NHS的情况下对所选细胞的RNA使用菌株特异性SRA探针,也无法在该菌株中检测到SRA转录本。

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