Characterisation of a fatty acid and retinol binding protein orthologue from the hookworm Ancylostoma ceylanicum.
Characterisation of a fatty acid and retinol binding protein orthologue from the hookworm Ancylostoma ceylanicum.
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DOI：
10.1016/j.ijpara.2009.06.005
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发表时间：
2009-12
影响因子：
4
通讯作者：
Cappello M
中科院分区：
文献类型：
--
作者：
Fairfax KC;Vermeire JJ;Harrison LM;Bungiro RD;Grant W;Husain SZ;Cappello M
钩虫是一种食血肠道线虫，在资源有限的国家感染了近10亿人，是贫血和营养不良的主要原因。与其他线虫一样，钩虫缺乏从头合成必需脂肪酸的能力，因此必须从外源来源获得这些脂肪酸。从钩虫成虫mRNA中扩增了一个推定的锡兰钩虫脂肪酸和视黄醇结合蛋白-1（AceFAR-1）的cDNA。使用定量逆转录酶真实的时间-PCR的研究表明，AceFAR-1转录本是最丰富的寄生虫的最早发育阶段，并在女性比男性更大。使用体外测定，重组AceFAR-1（rAceFAR-1）被证明结合个别脂肪酸的平衡解离常数在低微摩尔范围内。离体培养的活蠕虫摄取脂肪酸的模式与rAceFAR-1的体外结合特征相似，提高了天然蛋白质可能参与A.锡兰与仅用抗原或佐剂免疫的对照相比，用rAceFAR-1和粘膜佐剂霍乱毒素口服免疫的动物表现出肠蠕虫负荷的统计学显著（40-47%）降低。总之，这些数据表明AceFAR-1在钩虫生物学中的潜在作用，使其成为药物和疫苗开发的潜在有价值的靶点。
Hookworms, bloodfeeding intestinal nematodes, infect nearly one billion people in resource limited countries and are a leading cause of anemia and malnutrition. Like other nematodes, hookworms lack the capacity to synthesize essential fatty acids de novo and therefore must acquire those from exogenous sources. The cDNA corresponding to a putative Ancylostoma ceylanicum fatty acid and retinol binding protein-1 (AceFAR-1) was amplified from adult hookworm mRNA. Studies using quantitative reverse transcriptase real time-PCR demonstrate that AceFAR-1 transcripts are most abundant in the earliest developmental stages of the parasite, and greater in females than males. Using in vitro assays, the recombinant AceFAR-1 (rAceFAR-1) was shown to bind individual fatty acids with equilibrium dissociation constants in the low micromolar range. The pattern of fatty acid uptake by live adult worms cultured ex vivo was similar to the in vitro binding profile of rAceFAR-1, raising the possibility that the native protein may be involved in acquisition of fatty acids by A. ceylanicum. Animals vaccinated orally with rAceFAR-1 and the mucosal adjuvant cholera toxin exhibited a statistically significant (40–47%) reduction in intestinal worm burden compared with controls immunized with antigen or adjuvant alone. Together, these data suggest a potential role for AceFAR-1 in hookworm biology, making it a potentially valuable target for drug and vaccine development.
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影响因子：
1.5
作者：
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影响因子：
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