Geographic separation of domestic and wild strains of Toxoplasma gondii in French Guiana correlates with a monomorphic version of chromosome1a.

Geographic separation of domestic and wild strains of Toxoplasma gondii in French Guiana correlates with a monomorphic version of chromosome1a.
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DOI:
10.1371/journal.pntd.0003182
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发表时间:
2014-09
影响因子:
3.8
通讯作者:
Sibley LD
Sibley LD
中科院分区:
医学2区
文献类型:
--
作者:
Khan A;Ajzenberg D;Mercier A;Demar M;Simon S;Dardé ML;Wang Q;Verma SK;Rosenthal BM;Dubey JP;Sibley LD

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以往的研究强调了T.产自法属圭亚那的弓形虫。虽然来自沿海、人类适应环境(所谓的人类化)的菌株类似于在加勒比其他地区发现的菌株,但从内陆丛林环境收集的菌株在遗传上相当多样化。为了更好地了解这些不同菌株类型的组成,我们对T。来自法属圭亚那的弓形虫菌株,包括染色体1a(Chr1a)的分析,其通常在遗传上不同的谱系中共享为单个单态单倍型。选择性中性基因的内含子序列的比较表明,人源化菌株是最密切相关的克隆III型菌株从北美,虽然更广泛的RFLP分析表明,他们是自然的杂交种。相比之下,从丛林中分离出来的菌株在遗传上非常多样化。值得注意的是,几乎所有的人源化菌株含有单态版本的Chr1a,而野生菌株是非常分歧的。单态Chr1a的存在与家猫中更大的传播密切相关,尽管有几个例外,表明其他因素也有贡献。人源化菌株在实验室小鼠中的毒力也各不相同,这种模式不能用以前确定的毒力因子的简单组合来解释,这表明其他遗传决定因素影响致病性。我们的研究强调了人源化和野生型T.法属圭亚那的弓形虫,并提供额外的证据表明,Chr1a的存在与不同地理区域内广泛不同的谱系的成功扩张有关。Chr1a在人源化环境中的优势表明,它可能赋予在这种环境中传播的优势,从而可能有助于致病性决定因素的传播。 弓形虫是一种广泛存在的动物寄生虫,很容易传播给人类。此前的研究表明,法属圭亚那丛林地区的人类感染通常相当严重,而大多数人类感染的特征是健康成年人的症状较轻。在这里,我们的特点是从法属圭亚那的菌株的遗传组成,并确认,虽然遗传上同质的菌株存在于人类化的环境中,高度分歧和致病性菌株被发现在丛林环境中。菌株类型的地理分离也反映在保守的基因组区域中,包括染色体1a(Chr1A)的单态版本,该版本先前与世界各地不同谱系的传播有关。携带单态Chr1a的菌株在家猫中表现出更大的传播潜力,这可能有助于它们在人类化环境中的流行。我们的研究结果还揭示了法属圭亚那分离株在实验室小鼠中的急性毒力存在很大差异,这些差异与先前定义的已知遗传机制不同。因此,某些菌株类型由于传播增强而在环境中扩展的能力也可能导致毒力决定因素的传播。
Previous studies have stressed the genetic divergence and high pathogenicity of strains of T. gondii from French Guiana. Although strains from coastal, human adapted environments (so called anthropized) resemble those found in other regions of the Caribbean, strains collected from inland jungle environment are genetically quite diverse. To better understand the composition of these distinct strain types, we undertook a more in depth analysis of T. gondii strains from French Guiana including profiling of chromosome 1a (Chr1a), which is often shared as a single monomorphic haplotype among lineages that are otherwise genetically distinct. Comparison of intron sequences from selectively neutral genes indicated that anthropized strains were most closely related to clonal type III strains from North America, although wider RFLP analysis revealed that they are natural hybrids. In contrast, strains isolated from the jungle were genetically very diverse. Remarkably, nearly all anthropized strains contained the monomorphic version of Chr1a while wild stains were extremely divergent. The presence of the monomorphic Chr1a strongly correlated with greater transmission in domestic cats, although there were several exceptions, indicating that other factors also contribute. Anthropized strains also varied in their virulence in laboratory mice, and this pattern could not be explained by the simple combination of previously identified virulence factors, indicating that other genetic determinants influence pathogenicity. Our studies underscore the marked genetic separation of anthropized and wild strains of T. gondii in French Guiana and provide additional evidence that the presence of Chr1a is associated with successful expansion of widely different lineages within diverse geographic areas. The predominance of Chr1a among strains in the anthropized environment suggests that it may confer an advantage for transmission in this environment, and thus potentially contribute to the spread of pathogenecity determinants. Toxoplasma gondii is a widespread parasite of animals that is easily transmitted to humans. Previous studies have shown that human infections in jungle areas of French Guiana are often quite severe, unlike most human infections that are characterized by mild symptoms in healthy adults. Here we characterized the genetic makeup of strains from French Guiana and confirm that while genetically homogeneous strains exist in anthropized environments, highly divergent and pathogenic isolates are found in jungle environments. The geographic separation of strain types is also mirrored in conserved genomic regions, including a monomorphic version of chromosome 1a (Chr1A), which has previously been associated with the spread of different lineages around the world. Strains harboring the monomorphic Chr1a showed greater potential for transmission in domestic cats, which may contribute to their prevalence in anthropized environments. Our findings also revealed large differences in acute virulence of French Guiana isolates in the laboratory mouse, and these differ from known genetic mechanisms that have been defined previously. Hence, the ability of some strain types to expand in the environment as a consequence of enhanced transmission may also lead to the spread of virulence determinants.
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发表时间: 2001-06-01
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