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整合遗传学和基因组学以确定控制艾美耳球虫属的新线索

Integrating genetics and genomics to identify new leads for the control of Eimeria spp.

作者信息

Shirley M W, Blake D, White S E, Sheriff R, Smith A L

机构信息

Institute for Animal Health, Compton Laboratory, Compton, Nr Newbury, Berks, UK.

出版信息

Parasitology. 2004;128 Suppl 1:S33-42. doi: 10.1017/S0031182004006845.

Abstract

Eimerian parasites display a biologically interesting range of phenotypic variation. In addition to a wide spectrum of drug-resistance phenotypes that are expressed similarly by many other parasites, the Eimeria spp. present some unique phenotypes. For example, unique lines of Eimeria spp. include those selected for growth in the chorioallantoic membrane of the embryonating hens egg or for faster growth (precocious development) in the mature host. The many laboratory-derived egg-adapted or precocious lines also share a phenotype of a marked attenuation of virulence, the basis of which is different as a consequence of the in ovo or in vivo selection procedures used. Of current interest is the fact that some wild-type populations of Eimeria maxima are characterized by an ability to induce protective immunity that is strain-specific. The molecular basis of phenotypes that define Eimeria spp. is now increasingly amenable to investigation, both through technical improvements in genetic linkage studies and the availability of a comprehensive genome sequence for the caecal parasite E. tenella. The most exciting phenotype in the context of vaccination and the development of new vaccines is the trait of strain-specific immunity associated with E. maxima. Recent work in this laboratory has shown that infection of two inbred lines of White Leghorn chickens with the W strain of E. maxima leads to complete protection to challenge with the homologous parasite, but to complete escape of the heterologous H strain, i.e. the W strain induces an exquisitely strain-specific protective immune response with respect to the H strain. This dichotomy of survival in the face of immune-mediated killing has been examined further and, notably, mating between a drug-resistant W strain and a drug-sensitive H strain leads to recombination between the genetic loci responsible for the specificity of protective immunity and resistance to the anticoccidial drug robenidine. Such a finding opens the way forward for genetic mapping of the loci responsible for the induction of protective immunity and integration with the genome sequencing efforts.

摘要

艾美耳属寄生虫表现出一系列在生物学上有趣的表型变异。除了许多其他寄生虫也同样表现出的广泛耐药表型外,艾美耳属物种还呈现出一些独特的表型。例如,艾美耳属物种的独特品系包括那些在胚胎期母鸡鸡蛋的绒毛尿囊膜上生长而选择出来的品系,或者是在成熟宿主体内生长更快(早熟发育)的品系。许多实验室培育的适应卵或早熟品系也都有一个毒力显著减弱的表型,由于所采用的卵内或体内选择程序不同,其减弱的基础也有所不同。目前令人感兴趣的是,一些最大艾美耳球虫的野生型种群具有诱导菌株特异性保护性免疫的能力。通过遗传连锁研究技术的改进以及盲肠寄生虫柔嫩艾美耳球虫完整基因组序列的可得性,现在越来越便于对定义艾美耳属物种的表型的分子基础进行研究。在疫苗接种和新疫苗研发背景下,最令人兴奋的表型是与最大艾美耳球虫相关的菌株特异性免疫特性。本实验室最近的研究表明,用最大艾美耳球虫的W株感染两个白来航鸡近交系,可导致对同源寄生虫攻击的完全保护,但对异源H株则完全不产生保护作用,即W株针对H株诱导出了极其菌株特异性的保护性免疫反应。面对免疫介导的杀伤时这种生存差异已得到进一步研究,值得注意的是,耐药W株与药物敏感H株之间的交配导致了负责保护性免疫特异性和对抗球虫药罗苯哒唑耐药性的基因座之间的重组。这一发现为负责诱导保护性免疫的基因座的遗传定位以及与基因组测序工作的整合开辟了道路。

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