Ristow Paula, Bourhy Pascale, da Cruz McBride Flávia Weykamp, Figueira Claudio Pereira, Huerre Michel, Ave Patrick, Girons Isabelle Saint, Ko Albert I, Picardeau Mathieu
Unité de Biologie des Spirochètes, Institut Pasteur, Paris, France.
PLoS Pathog. 2007 Jul;3(7):e97. doi: 10.1371/journal.ppat.0030097.
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.
钩端螺旋体病的病原体问号钩端螺旋体的致病机制在很大程度上仍不清楚。这主要是由于缺乏对致病菌种进行基因操作的工具。在本研究中，我们鉴定了一个突变体，该突变体是通过将转座子Himar1插入到一个编码假定脂蛋白Loa22的基因中获得的，基于序列同一性，该脂蛋白具有一个预测的OmpA结构域。产生的突变体不表达Loa22，并且在钩端螺旋体病的豚鼠和仓鼠模型中毒力减弱，而基因互补菌株在Loa22表达和毒力方面得以恢复。我们的结果表明，Loa22在宿主感染期间表达并暴露于细胞表面。因此，Loa22是问号钩端螺旋体在动物模型中毒力所必需的，据我们所知，它是钩端螺旋体属中第一个通过基因定义的毒力因子。
