Cotter P A, Miller J F
Department of Microbiology and Immunology, School of Medicine, University of California, Los Angeles 90024.
Infect Immun. 1994 Aug;62(8):3381-90. doi: 10.1128/iai.62.8.3381-3390.1994.
Members of the Bordetella genus alternate between two distinct phenotypic phases in response to changes in their environment. This switch, termed phenotypic modulation, is mediated by the BvgAS sensory transduction system. We developed an animal model based on the interaction of Bordetella bronchiseptica with one of its natural hosts, the rabbit. To investigate the importance of BvgAS signal transduction, we constructed constitutive (RB53) and Bvg- (RB54) phase-locked derivatives of a wild-type strain, RB50. RB50 and RB53, but not RB54, established respiratory infections in B. bronchiseptica-free rabbits with an intranasal 50% infective dose of less than 200 organisms, and the course of the infection closely resembled that observed with naturally infected rabbits. Bacteria were recovered from the nasal cavity, larynx, trachea, and lungs in similar numbers from RB50- and RB53-infected rabbits, yet no pathology was detected by histological examination of lung and tracheal sections. The antibody responses in rabbits inoculated with RB50 or RB53 were quantitatively and qualitatively indistinguishable; high titers of antibodies were generated primarily against Bvg(+)-phase-specific antigens. No response against flagella, a Bvg- phase factor, was detected. Assessment of bacteria associated with alveolar macrophages indicated that only a small percentage of bacteria, if any, appear to be residing within lung macrophages. We also tested the ability of these strains to survive in a nutrient poor environment, conditions which may be encountered within certain niches in the host or in an environmental reservoir. The Bvg- phase was advantageous for growth under these conditions. Our results indicate the Bvg+ phase is sufficient for establishment of respiratory tract infection in the rabbit and the normal BvgAS-mediated response to environmental signals is not required during initial colonization. The Bvg- phase may play a role at later stages of infection, including persistence, transmission, or survival in the environment.
博德特氏菌属的成员会根据环境变化在两种不同的表型阶段之间交替。这种转变，称为表型调节，由BvgAS传感转导系统介导。我们基于支气管败血博德特氏菌与其天然宿主之一兔子的相互作用开发了一种动物模型。为了研究BvgAS信号转导的重要性，我们构建了野生型菌株RB50的组成型（RB53）和Bvg - （RB54）锁相衍生物。RB50和RB53，但不是RB54，在无支气管败血博德特氏菌的兔子中建立了呼吸道感染，鼻内50%感染剂量少于200个菌体，并且感染过程与自然感染兔子中观察到的非常相似。从RB50和RB53感染的兔子的鼻腔、喉部、气管和肺部回收的细菌数量相似，但通过肺和气管切片的组织学检查未检测到病理学变化。接种RB50或RB53的兔子中的抗体反应在数量和质量上没有区别；高滴度的抗体主要针对Bvg(+)阶段特异性抗原产生。未检测到针对鞭毛（一种Bvg - 阶段因子）的反应。与肺泡巨噬细胞相关的细菌评估表明，只有一小部分细菌（如果有的话）似乎存在于肺巨噬细胞内。我们还测试了这些菌株在营养贫乏环境中存活的能力，这种环境可能在宿主的某些生态位或环境储存库中遇到。Bvg - 阶段在这些条件下有利于生长。我们的结果表明，Bvg + 阶段足以在兔子中建立呼吸道感染，并且在初始定植期间不需要正常的BvgAS介导的对环境信号的反应。Bvg - 阶段可能在感染的后期阶段发挥作用，包括在环境中的持续存在、传播或存活。
