Previous in vitro works focusing on virulence determinants of the spirochete Leptospira implicated metalloproteinases as putative contributing factors to the pathogenicity of these bacteria. Those proteins have the capacity to degrade extracellular matrix components (ECM) and proteins of host's innate immunity, notably effectors of the complement system. In this study, we gained further knowledge on the role of leptolysin, one of the leptospiral‐secreted metalloproteinases, previously described as having a broad substrate specificity. We demonstrated that a proportion of human patients with mild leptospirosis evaluated in the current study produced antibodies that recognize leptolysin, thus indicating that the protease is expressed during host infection. Using recombinant protein and a knockout mutant strain, Manilae leptolysin−, we determined that leptolysin contributes to Leptospira interrogans serum resistance in vitro, likely by proteolysis of complement molecules of the alternative, the classical, the lectin, and the terminal pathways. Furthermore, in a hamster model of infection, the mutant strain retained virulence; however, infected animals had lower bacterial loads in their kidneys. Further studies are necessary to better understand the role and potential redundancy of metalloproteinases on the pathogenicity of this important neglected disease.

中文翻译：

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钩端螺旋体 钩端溶血素 导致血清耐药，但对急性感染不是必需的


先前的体外工作侧重于螺旋体钩端螺旋体的毒力决定因素，表明金属蛋白酶是这些细菌致病性的假定促成因素。这些蛋白质具有降解细胞外基质成分 （ECM） 和宿主先天免疫蛋白的能力，特别是补体系统的效应子。在这项研究中，我们进一步了解了钩端溶血素的作用，钩端溶血素是钩端螺旋体分泌的金属蛋白酶之一，以前描述为具有广泛的底物特异性。我们证明，在本研究中评估的一部分轻度钩端螺旋体病人类患者产生了识别钩端溶血素的抗体，从而表明蛋白酶在宿主感染期间表达。使用重组蛋白和敲除突变菌株 Manilae leptolysin-，我们确定钩端溶血素有助于在体外引起钩端螺旋体血清耐药性，这可能是通过替代、经典、凝集素和末端途径的补体分子的蛋白水解。此外，在仓鼠感染模型中，突变菌株保留了毒力;然而，受感染动物肾脏中的细菌负荷较低。需要进一步的研究来更好地了解金属蛋白酶对这种重要的被忽视疾病的致病性的作用和潜在的冗余。