Isolation of pathogenic Leptospira strains from naturally infected cattle in Uruguay reveals high serovar diversity, and uncovers a relevant risk for human leptospirosis

Leptospirosis is a neglected zoonosis with worldwide distribution. The causative agents are spirochete bacteria of the Leptospira genus, displaying huge diversity of serovars, the identity of which is critical for effective diagnosis and vaccination purposes. Among many other mammalian species, Leptospira infects cattle, eliciting acute signs in calves, and chronic disease in adult animals often leading to abortions. In South America, and including in Uruguay, beef and dairy export are leading sources of national income. Despite the importance of bovine health, food safety, and bovine-related dissemination of leptospirosis to humans, extremely limited information is available as to the identity of Leptospira species and serovars infecting cattle in Uruguay and the South American subcontinent. Here we report a multicentric 3-year study resulting in the isolation and detailed characterization of 40 strains of Leptospira spp. obtained from infected cattle. Combined serologic and molecular typing identified these isolates as L. interrogans serogroup Pomona serovar Kennewicki (20 strains), L. interrogans serogroup Canicola serovar Canicola (1 strain), L. borgpetersenii serogroup Sejroe serovar Hardjo (10 strains) and L. noguchii (9 strains). The latter showed remarkable phenotypic and genetic variability, belonging to 6 distinct serogroups, including 3 that did not react with a large panel of reference serogrouping antisera. Approximately 20% of cattle sampled in the field were found to be shedding pathogenic Leptospira in their urine, uncovering a threat for public health that is being largely neglected. The two L. interrogans serovars that we isolated from cattle displayed identical genetic signatures to those of human isolates that had previously been obtained from leptospirosis patients. This report of local Leptospira strains shall improve diagnostic tools and the understanding of leptospirosis epidemiology in South America. These strains could also be used as new components within bacterin vaccines to protect against the pathogenic Leptospira strains that are actually circulating, a direct measure to reduce the risk of human leptospirosis.

钩端螺旋体病（Leptospirosis）是一种全球分布的被忽视人兽共患病，其致病原为钩端螺旋体属（Leptospira）的螺旋体细菌，该菌拥有极为丰富的血清型（serovar）多样性，血清型的准确鉴定对于高效诊断与疫苗研发均至关重要。在诸多哺乳动物宿主中，钩端螺旋体可感染牛群，引发犊牛急性病症，成年动物则罹患慢性疾病，常导致流产。在南美洲，包括乌拉圭在内，牛肉与乳制品出口是国民经济的核心支柱产业。尽管牛群健康、食品安全以及牛源钩端螺旋体病向人类的传播均具有重大公共卫生意义，但目前关于乌拉圭及南美次大陆地区感染牛群的钩端螺旋体菌种及血清型的相关研究数据却极为匮乏。本研究为一项多中心、历时三年的科研项目，成功分离并完成了40株感染牛源钩端螺旋体（Leptospira spp.）菌株的详细鉴定与特征分析。结合血清学与分子分型技术，本次分离的菌株被鉴定为：问号钩端螺旋体（Leptospira interrogans）波摩那血清群（serogroup）肯尼威克血清型共20株、问号钩端螺旋体犬血清群犬血清型共1株、博氏钩端螺旋体（Leptospira borgpetersenii）塞罗罗血清群哈焦血清型共10株，以及野口钩端螺旋体（Leptospira noguchii）共9株。其中野口钩端螺旋体菌株展现出显著的表型与遗传异质性，可划分为6个独立的血清群，其中3个血清群无法与现有主流参考血清群抗血清发生交叉反应。野外采样的牛群中约20%可在尿液中排出致病性钩端螺旋体，这揭示了长期被忽视的公共卫生风险。本次从牛群分离的两株问号钩端螺旋体血清型，与此前从钩端螺旋体病患者体内分离的人类源菌株具有完全一致的遗传特征。本研究报道的本土钩端螺旋体菌株，将有助于优化南美洲地区钩端螺旋体病的诊断工具，并深化对其流行病学特征的认知。上述菌株还可作为灭活疫苗（bacterin vaccine）的新型组分，用于对抗当前流行的致病性钩端螺旋体菌株，这也是降低人类钩端螺旋体病感染风险的直接有效手段。