Characterization of acyl carrier protein and LytB in Babesia bovis apicoplast.
Characterization of acyl carrier protein and LytB in Babesia bovis apicoplast.
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DOI：
10.1016/j.molbiopara.2011.10.009
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发表时间：
2012-02
影响因子：
1.5
通讯作者：
Lau, Audrey O. T.
中科院分区：
文献类型：
--
作者：
Caballero, Marina C.;Pedroni, Monica J.;Palmer, Guy H.;Suarez, Carlos E.;Davitt, Christine;Lau, Audrey O. T.
对巴贝虫体内 II 型脂肪酸和类异戊二烯生物合成的研究导致在顶塑腔内鉴定出两种主要成分。 ► 这项研究展示了四膜巴贝斯顶端质体。 ► 牛巴贝虫顶端质体位于细胞核附近。 ► 酰基载体蛋白和 LytB 在牛巴贝虫中转录和翻译。 ► 牛巴贝虫中可能存在类异戊二烯生物合成。 ► 牛巴贝虫中可能不存在 II 型脂肪酸生物合成。顶复体是一种高度特化的细胞器，介导顶复门寄生虫生长和复制所需的功能。尽管不同寄生虫属和种之间的顶质体结构保守，但不同寄生虫和生命周期不同阶段的代谢需求也存在重大差异。为了具体比较具有共同和独特阶段的寄生虫之间的顶质体途径，我们对牛巴贝斯虫（在哺乳动物宿主中仅具有红细胞内无性阶段）的顶质体进行了表征，并将其与恶性疟原虫（具有无性红细胞内和肝脏阶段）的顶质体进行了比较。特别关注 II 型脂肪酸 (FASII) 和类异戊二烯 (MEP) 生物合成途径，我们搜索了途径成分和基因组内活性位点的保留，将关键成分 [酰基载体蛋白 (ACP) 和 4-羟基-3-甲基丁-2-烯基二磷酸还原酶 (LytB)] 定位到顶质体，并证明两种蛋白质的 N 端二分信号对于运输到顶质体是必需的且足够的流明。使用特定的药理学抑制，我们证明MEP生物合成可能被破坏，并且它的存在是牛博氏菌无性阶段的红细胞内生长所必需的，这与基因组途径分析及其在恶性疟原虫无性红细胞阶段的要求一致。相比之下，FASII生物合成可能存在也可能不存在，并且特定的药物靶标对牛伯氏杆菌红细胞内生长没有任何抑制作用，这与恶性疟原虫红细胞内生长缺乏需要是一致的。然而，基因组分析显示，牛芽孢杆菌中的 FASII 途径成分丢失，而恶性疟原虫的途径完整，但在需要时（肝脏阶段）被调节表达，而在不需要时（红细胞内阶段）则沉默。结果表明，顶端体生物合成途径的专门成型可以满足个体顶端复门寄生虫及其独特的细胞内生态位的需求。
Investigation of type II fatty acid and isoprenoid biosyntheses in Babesia resulted in the identification of two major components within the apicoplastic lumen. ► This study illustrates a four membrane babesid apicoplast. ► Babesia bovis apicoplast resides adjacent to the nucleus. ► Acyl carrier protein and LytB are transcribed and translated in Babesia bovis. ► Isoprenoid biosynthesis likely exists in Babesia bovis. ► Type II fatty acid biosynthesis may not be present in Babesia bovis. The apicoplast is a highly specialized organelle that mediates required functions in the growth and replication of apicomplexan parasites. Despite structural conservation of the apicoplast among different parasite genera and species, there are also critical differences in the metabolic requirements of different parasites and at different stages of the life cycle. To specifically compare apicoplast pathways between parasites that have both common and unique stages, we characterized the apicoplast in Babesia bovis, which has only intraerythrocytic asexual stages in the mammalian host, and compared it to that of Plasmodium falciparum, which has both asexual intraerythrocytic and hepatic stages. Specifically focusing on the type II fatty acid (FASII) and isoprenoid (MEP) biosynthesis pathways, we searched for pathway components and retention of active sites within the genome, localized key components [acyl carrier protein (ACP) and 4-hydroxy-3-methylbut-2-enyl diphosphate reductase (LytB)] to the apicoplast, and demonstrated that the N-terminal bipartite signals of both proteins are required and sufficient for trafficking to the apicoplast lumen. Using specific pharmacologic inhibition, we demonstrated that MEP biosynthesis may be disrupted and its presence is required for intraerythrocytic growth of B. bovis asexual stages, consistent with the genomic pathway analysis and with its requirement in the asexual erythrocytic stages of P. falciparum. In contrast, FASII biosynthesis may or may not be present and specific drug targets did not have any inhibitory effect to B. bovis intraerythrocytic growth, which is consistent with the lack of requirement for P. falciparum intraerythrocytic growth. However, genomic analysis revealed the loss of FASII pathway components in B. bovis whereas the pathway is intact for P. falciparum but regulated to be expressed when needed (hepatic stages) and silent when not (intraerythrocytic stages). The results indicate specialized molding of apicoplast biosynthetic pathways to meet the requirements of individual apicomplexan parasites and their unique intracellular niches.
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影响因子：
56.9
作者：
LEVY, MG;RISTIC, M
通讯作者：
RISTIC, M
影响因子：
4.1
作者：
Kapoor, M;Gopalakrishnapai, J;Surolia, A
通讯作者：
Surolia, A
影响因子：
4.9
作者：
Lizundia, Regina;Werling, Dirk;Ralph, Stuart A.
通讯作者：
Ralph, Stuart A.
DOI：
10.1073/pnas.0603391103
发表时间：
2006-08-29
影响因子：
11.1
作者：
Mazumdar, Jolly;Wilson, Emma H.;Striepen, Boris
通讯作者：
Striepen, Boris
影响因子：
30.3
作者：
Yu M;Kumar TR;Nkrumah LJ;Coppi A;Retzlaff S;Li CD;Kelly BJ;Moura PA;Lakshmanan V;Freundlich JS;Valderramos JC;Vilcheze C;Siedner M;Tsai JH;Falkard B;Sidhu AB;Purcell LA;Gratraud P;Kremer L;Waters AP;Schiehser G;Jacobus DP;Janse CJ;Ager A;Jacobs WR Jr;Sacchettini JC;Heussler V;Sinnis P;Fidock DA
通讯作者：
Fidock DA