Martinez de Tejada G, Cotter P A, Heininger U, Camilli A, Akerley B J, Mekalanos J J, Miller J F
Department of Microbiology and Immunology, UCLA School of Medicine, Los Angeles, California 90095-1747, USA.
Infect Immun. 1998 Jun;66(6):2762-8. doi: 10.1128/IAI.66.6.2762-2768.1998.
In Bordetella species, the BvgAS sensory transduction system mediates an alteration between the Bvg+ phase, characterized by expression of adhesins and toxins, and the Bvg- phase, characterized by the expression of motility and coregulated phenotypes in Bordetella bronchiseptica and by the expression of vrg loci in Bordetella pertussis. Since there is no known environmental or animal reservoir for B. pertussis, the causative agent of whooping cough, it has been assumed that this phenotypic alteration must occur within the human host during infection. Consistent with this hypothesis was the observation that a B. pertussis mutant, SK6, containing a TnphoA insertion mutation in a Bvg-repressed gene (vrg6) was defective for tracheal and lung colonization in a mouse model of respiratory infection (D. T. Beattie, R. Shahin, and J. Mekalanos, Infect. Immun. 60:571-577, 1992). This result was inconsistent, however, with the observation that a Bvg+ phase-locked B. bronchiseptica mutant was indistinguishable from the wild type in its ability to establish a persistent respiratory infection in rabbits and rats (P. A. Cotter and J. F. Miller, Infect. Immun. 62:3381-3390, 1994; B. J. Akerley, P. A. Cotter, and J. F. Miller, Cell 80:611-620, 1995). To directly address the role of Bvg-mediated signal transduction in B. pertussis pathogenesis, we constructed Bvg+ and Bvg- phase-locked mutants and compared them with the wild type for their ability to colonize the respiratory tracts of mice. Our results show that the Bvg+ phase of B. pertussis is necessary and sufficient for respiratory infection. By constructing a strain with a deletion in the bvgR regulatory locus, we also show that ectopic expression of Bvg- phase phenotypes decreases the efficiency of colonization, underscoring the importance of Bvg-mediated repression of gene expression in vivo. Finally, we show that the virulence defect present in strain SK6 cannot be attributed to the vrg6 mutation. These data contradict an in vivo role for the Bvg- phase of B. pertussis.
在博德特氏菌属中，BvgAS 信号转导系统介导了 Bvg⁺ 相和 Bvg⁻ 相之间的转变。Bvg⁺ 相的特征是表达黏附素和毒素，Bvg⁻ 相在支气管败血博德特氏菌中的特征是表达运动性和共调控表型，在百日咳博德特氏菌中的特征是表达 vrg 基因座。由于百日咳的病原体百日咳博德特氏菌没有已知的环境或动物储存宿主，因此推测这种表型改变必定发生在人类宿主感染期间。与该假设一致的是，观察到一株百日咳博德特氏菌突变体 SK6，其在一个受 Bvg 抑制的基因（vrg6）中含有一个 TnphoA 插入突变，在呼吸道感染的小鼠模型中气管和肺部定殖存在缺陷（D. T. Beattie、R. Shahin 和 J. Mekalanos，《感染与免疫》60:571 - 577，1992 年）。然而，这一结果与以下观察结果不一致：一个锁定在 Bvg⁺ 相的支气管败血博德特氏菌突变体在兔和大鼠中建立持续性呼吸道感染的能力与野生型没有区别（P. A. Cotter 和 J. F. Miller，《感染与免疫》62:3381 - 3390，1994 年；B. J. Akerley、P. A. Cotter 和 J. F. Miller，《细胞》80:611 - 620，1995 年）。为了直接研究 Bvg 介导的信号转导在百日咳博德特氏菌致病机制中的作用，我们构建了锁定在 Bvg⁺ 相和 Bvg⁻ 相的突变体，并将它们与野生型在定殖小鼠呼吸道的能力方面进行比较。我们的结果表明，百日咳博德特氏菌的 Bvg⁺ 相对呼吸道感染是必要且充分的。通过构建一个在 bvgR 调控基因座有缺失的菌株，我们还表明异位表达 Bvg⁻ 相表型会降低定殖效率，强调了 Bvg 介导的基因表达抑制在体内的重要性。最后，我们表明菌株 SK6 中存在的毒力缺陷不能归因于 vrg6 突变。这些数据与百日咳博德特氏菌 Bvg⁻ 相在体内的作用相矛盾。
