The OmpA-like protein Loa22 is essential for leptospiral virulence.
The OmpA-like protein Loa22 is essential for leptospiral virulence.
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OMPA样蛋白LOA22对于钩端螺旋力毒力至关重要。
DOI：
10.1371/journal.ppat.0030097
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发表时间：
2007-07
期刊：
影响因子：
6.7
通讯作者：
Picardeau, Mathieu
中科院分区：
文献类型：
--
作者：
Ristow, Paula;Bourhy, Pascale;da Cruz McBride, Flavia Weykamp;Figueira, Claudio Pereira;Huerre, Michel;Ave, Patrick;Girons, Isabelle Saint;Ko, Albert I;Picardeau, Mathieu
问号钩端螺旋体（钩端螺旋体病的病原体）的致病机制仍然很大程度上未知。这主要是由于缺乏对致病物种进行基因操作的工具。在这项研究中，我们表征了通过将转座子 Himar1 插入编码假定脂蛋白 Loa22 的基因中获得的突变体，该基因具有基于序列同一性的预测 OmpA 结构域。所得突变体不表达 Loa22，并且在钩端螺旋体病的豚鼠和仓鼠模型中毒力减弱，而基因补充菌株的 Loa22 表达和毒力得到恢复。我们的结果表明 Loa22 在宿主感染期间表达并暴露在细胞表面。因此，Loa22 对于动物模型中问号钩端螺旋体的毒力是必需的，据我们所知，Loa22 代表了钩端螺旋体物种中第一个基因定义的毒力因子。螺旋体包括医学上重要的病原体，例如莱姆病、梅毒和钩端螺旋体病的病原体，构成了进化上独特的细菌群。钩端螺旋体病是一种人畜共患疾病，每年导致全世界人类和动物的高死亡率和发病率。 2007 年是钩端螺旋体病病原体问号钩端螺旋体发现一百周年。到目前为止，钩端螺旋体带来的遗传障碍（主要是产生目标突变体的困难）阻碍了毒力基因的鉴定。在这项研究中，我们描述了致病性钩端螺旋体中的一种无毒突变体，该突变体是通过破坏 loa22 获得的，loa22 是编码含有 OmpA 结构域的外膜蛋白的基因。这种突变导致豚鼠模型中出现无毒突变体，将 loa22 重新引入突变体中恢复了钩端螺旋体杀死豚鼠的能力。因此，我们的结果表明 loa22 是一种毒力决定因子，据我们所知，这是第一个针对该病原体确定的毒力决定因子。
Pathogenic mechanisms of Leptospira interrogans, the causal agent of leptospirosis, remain largely unknown. This is mainly due to the lack of tools for genetic manipulations of pathogenic species. In this study, we characterized a mutant obtained by insertion of the transposon Himar1 into a gene encoding a putative lipoprotein, Loa22, which has a predicted OmpA domain based on sequence identity. The resulting mutant did not express Loa22 and was attenuated in virulence in the guinea pig and hamster models of leptospirosis, whereas the genetically complemented strain was restored in Loa22 expression and virulence. Our results show that Loa22 was expressed during host infection and exposed on the cell surface. Loa22 is therefore necessary for virulence of L. interrogans in the animal model and represents, to our knowledge, the first genetically defined virulence factor in Leptospira species. The spirochetes, which include medically important pathogens such as the causative agents of Lyme disease, syphilis, and leptospirosis, constitute an evolutionarily unique group of bacteria. Leptospirosis is a zoonotic disease that causes a high rate of mortality and morbidity in humans and animals throughout the world each year. The year 2007 marks the centenary of the discovery of the causative agent of leptospirosis, Leptospira interrogans. Until now, the genetic obstacles posed by leptospires (principally, the difficulties in generating targeted mutants) have hampered the identification of virulence genes. In this study, we describe an avirulent mutant in a pathogenic Leptospira that was obtained via disruption of loa22, a gene that encodes an outer membrane protein containing an OmpA domain. This mutation resulted in an avirulent mutant in the guinea pig model, and reintroduction of loa22 into the mutant restored Leptospira's ability to kill guinea pigs. Our results therefore indicate that loa22 is a virulence determinant that is, to our knowledge, the first identified for this pathogen.