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对三种毒力较强的印度钩端螺旋体的全基因组测序和从头组装。

Whole genome sequencing and de novo assembly of three virulent Indian isolates of Leptospira.

机构信息

Gujarat State Biotechnology Mission, Department of Science & Technology, Government of Gujarat, Gandhinagar 382011, India; Gujarat Biotechnology Research Centre, Department of Science & Technology, Government of Gujarat, Gandhinagar 382011, India; Department of Botany, Bioinformatics and Climate Change, University School of Science, Gujarat University, Ahmedabad 380009, India.

Gujarat State Biotechnology Mission, Department of Science & Technology, Government of Gujarat, Gandhinagar 382011, India; Gujarat Biotechnology Research Centre, Department of Science & Technology, Government of Gujarat, Gandhinagar 382011, India.

出版信息

Infect Genet Evol. 2020 Nov;85:104579. doi: 10.1016/j.meegid.2020.104579. Epub 2020 Oct 2.

DOI:10.1016/j.meegid.2020.104579
PMID:33017688
Abstract

Leptospirosis is a re-emerging bacterial zoonosis caused by pathogenic Leptospira, with a worldwide distribution and becoming a major public health concern. Prophylaxis of this disease is difficult due to several factors such as non-specific variable clinical manifestation, presence of a large number of serovar, species and asymptomatic reservoir hosts, lack of proper diagnostics and vaccines. Despite its global importance and severity of the disease, knowledge about the molecular mechanism of pathogenesis and evolution of pathogenic species of Leptospira remains limited. In this study, we sequenced and analyzed three highly pathogenic species of Indian isolates of Leptospira (interrogans, santarosai, and kirschneri). Additionally, we identified some virulence-related and CRISPR-Cas genes. The virulent analysis showed 232 potential virulence factors encoding proteins in L. interrogans strain Salinem and L. santarosai strain M-4 genome. While the genome of L. kirschneri strain Wumalasena was predicted to encode 198 virulence factor proteins. The variant calling analysis revealed 1151, 19,786, and 22,996 single nucleotide polymorphisms (SNPs) for L. interrogans strain Salinem, L. kirschneri strain Wumalasena and L. santarosai strain M-4, respectively, with a maximum of 5315 missense and 12,221 synonymous mutations for L. santarosai strain M-4. The structural analyses of genomes indicated potential evidence of inversions and structural rearrangment in all three genomes. The availability of these genome sequences and in silico analysis of Leptospira will provide a basis for a deeper understanding of their molecular diversity and pathogenesis mechanism, and further pave a way towards proper management of the disease.

摘要

钩端螺旋体病是一种由致病性钩端螺旋体引起的重新出现的细菌性人畜共患病,分布广泛,已成为主要的公共卫生关注点。由于临床症状不典型、存在大量血清型、物种和无症状储存宿主、缺乏适当的诊断和疫苗等多种因素,该病的预防较为困难。尽管该病具有全球性重要性和严重性,但对致病性钩端螺旋体的发病机制和进化的分子机制的了解仍然有限。在这项研究中,我们对三种来自印度的高致病性钩端螺旋体(问号钩端螺旋体、圣塔罗莎钩端螺旋体和克里希纳钩端螺旋体)进行了测序和分析。此外,我们还鉴定了一些与毒力相关和 CRISPR-Cas 基因。毒力分析显示,在 L. interrogans 菌株 Salinem 和 L. santarosai 菌株 M-4 的基因组中,有 232 个潜在的毒力因子编码蛋白。而 L. kirschneri 菌株 Wumalasena 的基因组则预测编码 198 个毒力因子蛋白。变异调用分析显示,L. interrogans 菌株 Salinem、L. kirschneri 菌株 Wumalasena 和 L. santarosai 菌株 M-4 的基因组分别有 1151、19786 和 22996 个单核苷酸多态性(SNP),其中 L. santarosai 菌株 M-4 的错义突变最多,为 5315 个,同义突变最多,为 12221 个。基因组的结构分析表明,这三个基因组中都存在潜在的倒位和结构重排证据。这些基因组序列的可用性和钩端螺旋体的计算机分析将为深入了解其分子多样性和发病机制提供基础,并进一步为疾病的适当管理铺平道路。

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