VirB3 to VirB6 and VirB8 to VirB11, but not VirB7, are essential for mediating persistence of Brucella in the reticuloendothelial system

VirB3 to VirB6 and VirB8 to VirB11, but not VirB7, are essential for mediating persistence of Brucella in the reticuloendothelial system
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DOI:
10.1128/jb.00406-08
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发表时间:
2008-07-01
影响因子:
3.2
通讯作者:
Tsolis, Renee M.
Tsolis, Renee M.
中科院分区:
生物学3区
文献类型:
--
作者:
den Hartigh, Andreas B.;Rolan, Hortensia G.;Tsolis, Renee M.

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流产布鲁氏菌virB位点包含12个开放阅读框,称为virB1至virB12,编码IV型分泌系统。virB基因座的极性突变显著降低了流产芽孢杆菌在培养巨噬细胞中存活或在小鼠器官中持续存在的能力。virB2基因的非极性缺失会降低培养巨噬细胞和小鼠器官的存活率,而virB基因的非极性缺失只会降低巨噬细胞的存活率,而virB12对于这两种毒力特征都是必不可少的。在这里,我们研究了virB基因座中剩余基因在巨噬细胞存活和小鼠毒力中的作用。构建并鉴定了携带virB3、virB4、virB5、virB6、virB7、virB8、virB9、virB10或virB] I基因非极性缺失的突变体。所有突变都降低了B. abortus在J774A.1小鼠巨噬细胞样细胞中的存活能力,其程度与整个virB位点的缺失所造成的程度相似。virB3、virB4、virB5、virB6、virB8、virB9、virB10和virB11的缺失显著降低了感染后8周小鼠脾脏中流产芽孢杆菌的存活能力。有趣的是,virB7的缺失并未降低B. abortus在小鼠脾脏中持续存在的能力。我们得出结论,virB2、virB3、virB4、virB5、virB6、virB8、virB9、virB10和virB11是流产芽孢杆菌在小鼠体内的毒力所必需的,而virB、virB7和virB12基因编码的功能在该动物模型的器官中不需要。
The Brucella abortus virB locus contains 12 open reading frames, termed virB1 through virB12, which encode a type IV secretion system. Polar mutations in the virB locus markedly reduce the ability of B. abortus to survive in cultured macrophages or to persist in organs of mice. While a nonpolar deletion of the virB2 gene reduces survival in cultured macrophages and in organs of mice, a nonpolar deletion of virB] only reduces survival in macrophages, whereas virB12 is dispensable for either virulence trait. Here we investigated the role of the remaining genes in the virB locus during survival in macrophages and virulence in mice. Mutants carrying nonpolar deletions of the virB3, virB4, virB5, virB6, virB7, virB8, virB9, virB10, or virB] I gene were constructed and characterized. All mutations reduced the ability of B. abortus to survive in J774A.1 mouse macrophage-like cells to a degree similar to that caused by a deletion of the entire virB locus. Deletion of virB3, virB4, virB5, virB6, virB8, virB9, virB10, or virB11 markedly reduced the ability of B. abortus to persist in the spleens of mice at 8 weeks after infection. Interestingly, deletion of virB7 did not reduce the ability of B. abortus to persist in spleens of mice. We conclude that virB2, virB3, virB4, virB5, virB6, virB8, virB9, virB10, and virB11 are essential for virulence of B. abortus in mice, while functions encoded by the virB], virB7, and virB12 genes are not required for persistence in organs with this animal model.