Departamento de Microbiología y Genética, Universidad de Salamanca, Salamanca, Spain.
Infect Immun. 2012 May;80(5):1783-93. doi: 10.1128/IAI.06257-11. Epub 2012 Mar 5.
Brucella ovis is a rough bacterium--lacking O-polysaccharide chains in the lipopolysaccharide--that is virulent in its natural host and whose virulence mechanisms remain almost unexplored. In a search for additional traits that distinguish B. ovis from smooth Brucella, which require O-polysaccharide chains for virulence, we have analyzed the significance in B. ovis of the main virulence factors described for smooth Brucella. Attempts to obtain strains of virulent B. ovis strain PA that are mutated in the BvrR/BvrS two-component regulatory system were unsuccessful, suggesting the requirement of that system for in vitro survival, while the inactivation of bacA--in contrast to the results seen with smooth Brucella--did not affect splenic colonization in mice or behavior in J774.A1 murine macrophages. Defects in the synthesis of cyclic ß-1,2 glucans reduced the uptake of B. ovis PA in macrophages and, although the intracellular multiplication rate was unaffected, led to attenuation in mice. Growth of strains with mutations in the type IV secretion system (encoded by the virB operon) and the quorum-sensing-related regulator VjbR was severely attenuated in the mouse model, and although the mutant strains internalized like the parental strain in J774.A1 murine macrophages, they were impaired for intracellular replication. As described for B. melitensis, VjbR regulates the transcription of the virB operon positively, and the N-dodecanoyl-dl-homoserine lactone (C(12)-HSL) autoinducer abrogates this effect. In contrast, no apparent VjbR-mediated regulation of the fliF flagellar gene was observed in B. ovis, probably due to the two deletions detected upstream of fliF. These results, together with others reported in the text, point to similarities between rough virulent B. ovis and smooth Brucella species as regards virulence but also reveal distinctive traits that could be related to the particular pathogenicity and host tropism characteristics of B. ovis.
绵羊布鲁氏菌是一种粗糙型细菌，其脂多糖中缺乏 O-多糖链，在其自然宿主中具有毒力，但其毒力机制几乎未被探索。在寻找区分光滑布鲁氏菌的其他特征时，我们分析了在粗糙型布鲁氏菌中描述的主要毒力因子的重要性。光滑布鲁氏菌需要 O-多糖链才能具有毒力，尝试获得突变 BvrR/BvrS 双组分调节系统的强毒力绵羊布鲁氏菌 PA 菌株的尝试均未成功，这表明该系统对于体外存活是必需的，而 bacA 的失活——与光滑布鲁氏菌的结果相反——并不影响小鼠脾脏定植或 J774.A1 鼠巨噬细胞中的行为。环状β-1,2 葡聚糖合成缺陷降低了 B. ovis PA 在巨噬细胞中的摄取，尽管细胞内倍增率不受影响，但导致小鼠减毒。在小鼠模型中，缺失型分泌系统（由 virB 操纵子编码）和群体感应相关调节因子 VjbR 的菌株的生长严重衰减，尽管突变菌株在 J774.A1 鼠巨噬细胞中像亲本菌株一样内化，但它们在细胞内复制方面受到损害。与 B. melitensis 一样，VjbR 正向调节 virB 操纵子的转录，而 N-十二酰基-dl-高丝氨酸内酯 (C(12)-HSL) 自动诱导物则削弱了这种效应。相反，在 B. ovis 中未观察到明显的 VjbR 介导的 fliF 鞭毛基因调节，这可能是由于在 fliF 上游检测到两个缺失。这些结果与本文中报道的其他结果一起，表明粗糙毒力型 B. ovis 与光滑布鲁氏菌物种在毒力方面具有相似性，但也揭示了一些独特的特征，这些特征可能与 B. ovis 的特定致病性和宿主嗜性特征有关。
