BVGAS-MEDIATED SIGNAL-TRANSDUCTION - ANALYSIS OF PHASE-LOCKED REGULATORY MUTANTS OF BORDETELLA-BRONCHISEPTICA IN A RABBIT MODEL
BVGAS-MEDIATED SIGNAL-TRANSDUCTION - ANALYSIS OF PHASE-LOCKED REGULATORY MUTANTS OF BORDETELLA-BRONCHISEPTICA IN A RABBIT MODEL
复制标题
bvgas 介导的信号转导--在兔模型中分析锁相调节突变体的博德特氏菌--布鲁氏菌
DOI：
10.1128/iai.62.8.3381-3390.1994
复制
发表时间：
1994-08-01
影响因子：
3.1
通讯作者：
MILLER, JF
中科院分区：
文献类型：
--
作者：
COTTER, PA;MILLER, JF
博德特氏菌属的成员在两个不同的表型阶段之间交替，以响应其环境的变化。这种开关称为表型调节，由BvgAS感觉转导系统介导。我们建立了一种基于支气管败血波氏杆菌与其天然宿主兔相互作用的动物模型。为了研究BvgAS信号转导的重要性，我们构建了野生型菌株RB 50的组成型（RB 53）和Bvg（-）（RB 54）锁相衍生物。在B中，RB 50和RB 53（而非RB 53）建立了呼吸道感染。无支气管败血症的家兔，鼻内50%感染剂量小于200个微生物，感染过程与观察到的与自然感染的家兔非常相似。从RB 50和RB 53感染的家兔的鼻腔、喉、气管和肺中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。在接种RB 50或RB 53的家兔中，抗体应答在定量和定性上难以区分;主要针对Bvg（+）相特异性抗原产生高滴度抗体。未检测到对鞭毛（Bvg（-）相因子）的反应。对肺泡巨噬细胞相关细菌的评估表明，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的环境中生存的能力，这些条件可能会在宿主或环境水库的某些小生境中遇到。在这些条件下，Bvg（-）相有利于生长。我们的研究结果表明，Bvg（+）阶段是足够的建立呼吸道感染的兔子和正常的BvgAS介导的反应，环境信号是不需要在最初的殖民。Bvg（-）阶段可能在感染的后期发挥作用，包括持续性，传播或在环境中生存。
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 RB53, 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,vith 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 rule at later stages of infection, including persistence, transmission, or survival in the environment.