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Nuclear and mitochondrial genome sequencing of North-African Leishmania infantum isolates from cured and relapsed visceral leishmaniasis patients reveals variations correlating with geography and phenotype
Microbial Genomics ( IF 4.0 ) Pub Date : 2020-10-01 , DOI: 10.1099/mgen.0.000444
Giovanni Bussotti 1, 2 , Alia Benkahla 3 , Fakhri Jeddi 4, 5 , Oussama Souiaï 3 , Karim Aoun 6 , Gerald F Späth 2 , Aïda Bouratbine 6
Affiliation  

Although several studies have investigated genetic diversity of Leishmania infantum in North Africa, genome-wide analyses are lacking. Here, we conducted comparative analyses of nuclear and mitochondrial genomes of seven L. infantum isolates from Tunisia with the aim to gain insight into factors that drive genomic and phenotypic adaptation. Isolates were from cured (n=4) and recurrent (n=3) visceral leishmaniasis (VL) cases, originating from northern (n=2) and central (n=5) Tunisia, where respectively stable and emerging VL foci are observed. All isolates from relapsed patients were from Kairouan governorate (Centre); one showing resistance to the anti-leishmanial drug Meglumine antimoniate. Nuclear genome diversity of the isolates was analysed by comparison to the L. infantum JPCM5 reference genome. Kinetoplast maxi and minicircle sequences (1 and 59, respectively) were extracted from unmapped reads and identified by blast analysis against public data sets. The genome variation analysis grouped together isolates from the same geographical origins. Strains from the North were very different from the reference showing more than 34 587 specific single nucleotide variants, with one isolate representing a full genetic hybrid as judged by variant frequency. Composition of minicircle classes within isolates corroborated this geographical population structure. Read depth analysis revealed several significant gene copy number variations correlating with either geographical origin (amastin and Hsp33 genes) or relapse (CLN3 gene). However, no specific gene copy number variation was found in the drug-resistant isolate. In contrast, resistance was associated with a specific minicircle pattern suggesting Leishmania mitochondrial DNA as a potential novel source for biomarker discovery.

中文翻译:


对来自治愈和复发内脏利什曼病患者的北非婴儿利什曼原虫分离株进行核和线粒体基因组测序,揭示了与地理和表型相关的变异



尽管有几项研究调查了北非婴儿利什曼原虫的遗传多样性,但缺乏全基因组分析。在这里,我们对七个L的核和线粒体基因组进行了比较分析。婴儿从突尼斯分离出来,目的是深入了解驱动基因组和表型适应的因素。分离株来自已治愈 ( n = 4) 和复发 ( n = 3) 内脏利什曼病 (VL) 病例,源自突尼斯北部 ( n = 2) 和中部 ( n = 5),分别观察到稳定和新出现的 VL 病灶。所有复发患者的分离株均来自凯鲁万省(中部);一种对抗利什曼病药物锑酸葡甲胺显示出耐药性。通过与婴儿乳杆菌JPCM5 参考基因组进行比较,分析了分离株的核基因组多样性。从未映射的读数中提取动质体大环和小环序列(分别为 1 和 59),并通过针对公共数据集的爆炸分析进行鉴定。基因组变异分析将来自相同地理起源的分离株分组在一起。来自北方的菌株与参考菌株有很大不同,显示出超过 34 587 个特定的单核苷酸变异,其中一个分离株代表了根据变异频率判断的完整遗传杂种。分离株内小环类的组成证实了这种地理种群结构。读取深度分析揭示了与地理起源(amastin 和 Hsp33 基因)或复发(CLN3 基因)相关的几个显着的基因拷贝数变异。然而,在耐药菌株中没有发现特定的基因拷贝数变异。 相比之下,耐药性与特定的小环模式相关,表明利什曼原虫线粒体 DNA 是发现生物标志物的潜在新来源。
更新日期:2020-10-27
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