Analysis of the behavior of eryC mutants of Brucella suis attenuated in macrophages
Analysis of the behavior of eryC mutants of Brucella suis attenuated in macrophages
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DOI：
10.1128/iai.73.10.6782-6790.2005
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发表时间：
2005-10-01
影响因子：
3.1
通讯作者：
Köhler, S
中科院分区：
文献类型：
--
作者：
Burkhardt, S;de Bagüés, MPJ;Köhler, S
兼性细胞内病原体布鲁氏菌以其在专业和非专业吞噬细胞中复制的能力为特征，也会导致反刍动物流产。这种特性与胎盘中赤藓糖醇的存在有关，因为布鲁氏菌优先利用赤藓糖醇。赤藓操纵子编码参与赤藓糖醇代谢的酶，其与毒力的联系已被讨论。猪布鲁氏菌 eryC 中的等位基因交换突变体在体外对赤藓糖醇敏感，MIC 为 1 至 5 mM 赤藓糖醇。它们在巨噬细胞样细胞中的增殖减少了 50 至 90 倍，但突变体的互补恢复了野生型细胞内增殖水平以及使用赤藓糖醇作为唯一碳源的能力。在体内，eryC 突变体在受感染 BALB/c 小鼠脾脏中的定植程度显着低于野生型和补充菌株。有趣的是，另外自发耐受赤藓糖醇的eryC突变体仍然表现出与野生型相似的巨噬细胞内和鼠内复制。我们从结果中得出结论，赤藓糖醇不是巨噬细胞宿主细胞中病原体的必需碳源，但 eryC 基因的失活显着降低了猪双歧杆菌的巨噬细胞内和鼠内适应性。
The facultatively intracellular pathogen Brucella, characterized by its capacity to replicate in professional and non professional phagocytes, also causes abortion in ruminants. This property has been linked to the presence of erythritol in the placenta, as brucellae preferentially utilize erythritol. The ery operon encodes enzymes involved in erythritol metabolism, and a link with virulence has since been discussed. Allelic exchange mutants in eryC of Brucella suis were erythritol sensitive in vitro with a MIC of 1 to 5 mM of erythritol. Their multiplication in macrophage-like cells was 50- to 90-fold reduced, but complementation of the mutant restored wild-type levels of intracellular multiplication and the capacity to use erythritol as a sole carbon source. In vivo, the eryC mutant colonized the spleens of infected BALB/c mice to a significantly lower extent than the wild type and the complemented strain. Interestingly, eryC mutants that were in addition spontaneously erythritol tolerant nevertheless exhibited wild-type-like intramacrophagic and intramurine replication. We concluded from our results that erythritol was not an essential carbon source for the pathogen in the macrophage host cell but that the inactivation of the eryC gene significantly reduced the intramacrophagic and intramurine fitness of B. suis.