Departamento de Microbiología y Parasitología, Universidad de Navarra, Pamplona, Spain.
PLoS One. 2010 Apr 21;5(4):e10216. doi: 10.1371/journal.pone.0010216.
The two-component BvrR/BvrS system is essential for Brucella abortus virulence. It was shown previously that its dysfunction alters the expression of some major outer membrane proteins and the pattern of lipid A acylation. To determine the genes regulated by BvrR/BvrS, we performed a whole-genome microarray analysis using B. abortus RNA obtained from wild type and bvrR mutant cells grown in the same conditions.
METHODOLOGY/PRINCIPAL FINDINGS: A total of 127 differentially expressed genes were found: 83 were over expressed and 44 were less expressed in the bvrR mutant. Two operons, the phosphotransferase system and the maltose transport system, were down-regulated. Several genes involved in cell envelope or outer membrane biogenesis were differentially expressed: genes for outer membrane proteins (omp25a, omp25d), lipoproteins, LPS and fatty acid biosynthesis, stress response proteins, chaperones, flagellar genes, and twelve genes encoding ABC transport systems. Ten genes related with carbon metabolism (pckA and fumB among others) were up-regulated in the bvrR mutant, and denitrification genes (nirK, norC and nosZ) were also regulated. Notably, seven transcriptional regulators were affected, including VjbR, ExoR and OmpR that were less expressed in the bvrR mutant. Finally, the expression of eleven genes which have been previously related with Brucella virulence was also altered.
CONCLUSIONS/SIGNIFICANCE: All these data corroborate the impact of BvrR/BvrS on cell envelope modulation, confirm that this system controls the carbon and nitrogen metabolism, and suggest a cross-talk among some regulators to adjust the Brucella physiology to the shift expected to occur during the transit from the extracellular to the intracellular niche.
双组份 BvrR/BvrS 系统是布鲁氏菌属流产株毒力所必需的。先前的研究表明,其功能障碍会改变一些主要外膜蛋白的表达和脂 A 酰化模式。为了确定 BvrR/BvrS 调控的基因,我们使用在相同条件下生长的野生型和 bvrR 突变细胞的布鲁氏菌属 abortus RNA 进行了全基因组微阵列分析。
方法/主要发现:共发现 127 个差异表达基因:bvrR 突变体中 83 个基因过表达,44 个基因低表达。磷酸转移酶系统和麦芽糖转运系统两个操纵子下调。一些与细胞包膜或外膜生物发生相关的基因差异表达:外膜蛋白(omp25a、omp25d)、脂蛋白、LPS 和脂肪酸生物合成、应激反应蛋白、伴侣蛋白、鞭毛基因和 12 个 ABC 转运系统基因。pckA 和 fumB 等 10 个与碳代谢相关的基因在 bvrR 突变体中上调,硝酸盐还原基因(nirK、norC 和 nosZ)也受到调控。值得注意的是,有七个转录调节因子受到影响,包括在 bvrR 突变体中表达水平降低的 VjbR、ExoR 和 OmpR。最后,还改变了 11 个先前与布鲁氏菌属毒力相关的基因的表达。
结论/意义:所有这些数据都证实了 BvrR/BvrS 对细胞包膜调节的影响,证实该系统控制碳氮代谢,并表明一些调节剂之间存在交叉对话,以调整布鲁氏菌属的生理机能,以适应从细胞外到细胞内小生境的转变。