Mobile Elements.

Leptospira borgpetersenii is a causative agent of human leptospirosis, with the potential to lead to severe disease manifestations. The first published analysis of L. borgpetersenii, performed on two strains of serovar Hardjo (L550 and JB197), suggested that the L. borgpetersenii genome is in the process of genome decay with functional consequences leading to a more obligately host-dependent life cycle. Whole genome analysis has only been carried out on few strains of L. borgpetersenii, with limited closed genomes and comprehensive analyses. Herein we report the complete, circularized genomes of seven non-typeable Leptospira borgpetersenii isolates from human leptospirosis patients in Sri Lanka. These isolates (all identified as strain ST144) were found to be nearly identical by whole genome analysis; serotyping with serogroup-specific reference antisera was unreactive, suggesting that these are members of a novel serogroup/serovar. We show that the L. borgpetersenii isolated from humans in Sri Lanka show less genomic decay than previously reported isolates: fewer pseudogenes (N = 141) and insertion sequence (IS) elements (N = 46) compared to N = 248, N = 270, and N = 400 pseudogenes, and N = 121 and N = 116 IS elements in other published L. borgpetersenii Hardjo genomes (strains L550, JB197 and TC112). Compared to previously published L. borgpetersenii whole genome analyses showing two or three VM proteins in L. borgpetersenii isolates from cattle, rats and humans, we found that all of the human L. borgpetersenii isolates from Sri Lanka, including previously reported serovar Piyasena, have four encoded VM proteins, one ortholog of L. interrogans Copenhageni LIC12339 (LA1402) and three orthologs of LIC12844 (LA0589). Our findings of fewer pseudogenes, IS elements, and expansion of the LIC12844 homologs of the PF07598 family in these human isolates suggests that this newly identified L. borgpetersenii serovar from Sri Lanka has unique pathogenicity. Comparative genome analysis and experimental studies of these L. borgpetersenii isolates offer deeper insights into the molecular and cellular mechanisms of leptospirosis pathogenesis.

博氏钩端螺旋体（Leptospira borgpetersenii）是人类钩端螺旋体病（Leptospirosis）的致病原之一，可引发严重的疾病表现。此前针对硬爪血清型（serovar Hardjo）的两株菌株（L550与JB197）开展的首次已发表博氏钩端螺旋体基因组分析显示，博氏钩端螺旋体基因组正处于衰退进程中，其功能变化使其宿主依赖型生命周期更为专性。目前针对博氏钩端螺旋体的全基因组分析仅在少数菌株中开展，且已完成闭合组装的基因组及全面分析均较为有限。本研究报道了7株从斯里兰卡人类钩端螺旋体病患者体内分离得到的不可分型博氏钩端螺旋体的完整环状基因组。这些分离株（均鉴定为ST144菌株）经全基因组分析显示几乎完全一致；采用血清群特异性参考抗血清进行血清分型时未出现反应，提示其属于新型血清群/血清型。研究发现，从斯里兰卡人类体内分离得到的博氏钩端螺旋体的基因组衰退程度低于此前报道的菌株：其假基因（pseudogene）数量为141个，插入序列（insertion sequence, IS）元件数量为46个；而其他已发表的博氏钩端螺旋体硬爪血清型菌株（L550、JB197与TC112）的假基因数量分别为248、270、400个，插入序列元件数量分别为121与116个。相较于此前已发表的博氏钩端螺旋体全基因组分析（该分析显示在牛、大鼠与人类分离的博氏钩端螺旋体菌株中存在2或3种可变膜蛋白（VM proteins）），本研究发现，所有从斯里兰卡人类体内分离得到的博氏钩端螺旋体分离株（包括此前报道的Piyasena血清型）均编码4种可变膜蛋白：其中1个为问号钩端螺旋体（Leptospira interrogans）哥本哈根株LIC12339（LA1402）的直系同源基因（ortholog），另外3个为LIC12844（LA0589）的直系同源基因。本研究中人类分离株的假基因与插入序列元件数量更少，且PF07598家族的LIC12844同源基因发生了扩增，这些发现提示，这一从斯里兰卡新鉴定出的博氏钩端螺旋体血清型具有独特的致病性。对这些博氏钩端螺旋体分离株开展比较基因组分析与实验研究，将为深入解析钩端螺旋体病发病的分子与细胞机制提供更深刻的见解。