Espiau Benoît, Vilhena Virginia, Cuvillier Armelle, Barral Aldina, Merlin Gilles
Université de Bordeaux, Laboratoire de Génomique Fonctionnelle des Trypanosomatidés, Bordeaux, France.
LabEx Corail, Papetoai, Moorea, Polynésie Française.
Mem Inst Oswaldo Cruz. 2017 Jan 1;112(1):44-52. doi: 10.1590/0074-02760160280.
Leishmania are protozoan parasites that show remarkable diversity, as revealed by the various clinical forms of leishmaniasis, which can range from mild skin lesions to severe metastatic cutaneous/mucosal lesions. The exact nature and extent of Leishmania phenotypic diversity in establishing infection is not fully understood. In order to try to understand some aspects of this diversity, we subcutaneously infected BALB/c mice with first and second generation subclones of a L. amazonensis strain isolated from a patient (BA125) and examined in vivo lesion growth rate and antimony susceptibility. In vivo fast-, medium- and slow-growing subclones were obtained; moreover, fast-growing subclones could generate slow-growing subclones and inversely, revealing the continuous generation of diversity after passage into mice. No antimony-resistant subclone appeared, probably a rare occurrence. By tagging subclone cells with a L. amazonensis genomic cosmid library, we found that only a very small number of founding cells could produce lesions. Leishmania clones transfected with in vivo selected individual cosmids were also diverse in terms of lesion growth rate, revealing the cosmid-independent intrinsic characteristics of each clone. Our results suggest that only a few of the infecting parasites are able to grow and produce lesions; later, within the cell mixture of each lesion, there coexist several parasite populations with different potentialities to grow lesions during the next infection round. This may reflect a sort of programmed heterogeneity of individual parasites, favoring the survival of some individuals in various environmental conditions.
利什曼原虫是原生动物寄生虫，表现出显著的多样性，这一点从利什曼病的各种临床形式中可见一斑，其范围从轻度皮肤损伤到严重的转移性皮肤/粘膜损伤。在建立感染过程中利什曼原虫表型多样性的确切性质和程度尚未完全明了。为了尝试理解这种多样性的某些方面，我们用从一名患者分离出的亚马逊利什曼原虫菌株（BA125）的第一代和第二代亚克隆皮下感染BALB/c小鼠，并检测体内损伤生长速率和锑敏感性。在体内获得了快速生长、中等生长和缓慢生长的亚克隆；此外，快速生长的亚克隆可产生缓慢生长的亚克隆，反之亦然，这表明在接种到小鼠体内后多样性不断产生。未出现抗锑亚克隆，可能这是一种罕见的情况。通过用亚马逊利什曼原虫基因组黏粒文库标记亚克隆细胞，我们发现只有极少数起始细胞能够产生损伤。用体内选择的单个黏粒转染的利什曼原虫克隆在损伤生长速率方面也存在差异，这揭示了每个克隆不依赖黏粒的内在特征。我们的结果表明，只有少数感染性寄生虫能够生长并产生损伤；随后，在每个损伤的细胞混合物中，存在几个具有不同潜力在下次感染周期中生长损伤的寄生虫群体。这可能反映了个体寄生虫的一种程序性异质性，有利于一些个体在各种环境条件下存活。
