Merkel T J, Stibitz S, Keith J M, Leef M, Shahin R
National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892, USA.
Infect Immun. 1998 Sep;66(9):4367-73. doi: 10.1128/IAI.66.9.4367-4373.1998.
Whooping cough is an acute respiratory disease caused by the small, gram-negative bacterium Bordetella pertussis. B. pertussis expresses several factors that contribute to its ability to cause disease. These factors include surface-associated molecules, which are involved in the adherence of the organism to respiratory epithelial cells, as well as several extracellular toxins that inhibit host defenses and induce damage to host tissues. The expression of virulence factors in B. pertussis is dependent upon the bvg locus, which consists of three genes: bvgA, bvgS, and bvgR. The bvgAS genes encode a two-component regulatory system consisting of a sensor protein, BvgS, and a transcriptional activator, BvgA. Upon modification by BvgS, BvgA binds to the promoter regions of the bvg-activated genes and activates transcription. One of the bvg-activated genes, bvgR, is responsible for the regulation of the bvg-repressed genes, the functions of which are unknown. The fact that these genes are regulated by the bvg locus suggests that they play a role in the pathogenesis of the bacterium. In order to evaluate the contribution of bvg-mediated regulation to the virulence of B. pertussis and determine if expression of the bvg-repressed genes is required for the virulence of B. pertussis, we examined the ability of B. pertussis mutants, defective in their ability to regulate the expression of the bvg-activated and/or the bvg-repressed genes, to cause disease in the mouse aerosol challenge model. Our results indicate that the bvgR-mediated regulation of gene expression contributes to respiratory infection of mice.
百日咳是一种由革兰氏阴性小杆菌百日咳博德特氏菌引起的急性呼吸道疾病。百日咳博德特氏菌表达多种有助于其致病的因子。这些因子包括与表面相关的分子，它们参与该菌对呼吸道上皮细胞的黏附，以及几种抑制宿主防御并诱导宿主组织损伤的细胞外毒素。百日咳博德特氏菌毒力因子的表达依赖于bvg位点，该位点由三个基因组成：bvgA、bvgS和bvgR。bvgAS基因编码一个双组分调节系统，由传感蛋白BvgS和转录激活因子BvgA组成。经BvgS修饰后，BvgA与bvg激活基因的启动子区域结合并激活转录。bvg激活基因之一bvgR负责调节bvg抑制基因，其功能尚不清楚。这些基因受bvg位点调控这一事实表明它们在该菌的致病过程中发挥作用。为了评估bvg介导的调节对百日咳博德特氏菌毒力的贡献，并确定百日咳博德特氏菌的毒力是否需要bvg抑制基因的表达，我们检测了在调节bvg激活基因和/或bvg抑制基因表达能力上有缺陷的百日咳博德特氏菌突变体在小鼠气溶胶攻击模型中致病的能力。我们的结果表明，bvgR介导的基因表达调节有助于小鼠的呼吸道感染。
