Pregenomic comparative analysis between Bordetella bronchiseptica RB50 and Bordetella pertussis Tohama I in murine models of respiratory tract infection
Pregenomic comparative analysis between Bordetella bronchiseptica RB50 and Bordetella pertussis Tohama I in murine models of respiratory tract infection
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DOI：
10.1128/iai.67.11.6109-6118.1999
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发表时间：
1999-11-01
影响因子：
3.1
通讯作者：
Miller, JF
中科院分区：
文献类型：
--
作者：
Harvill, ET;Cotter, PA;Miller, JF
我们在这里描述了小鼠呼吸道感染的百日咳博德特氏菌和支气管败血博德特氏菌菌株，其基因组目前正在测序（Tohama I和RB 50，分别）并排比较。B。百日咳和B.支气管炎最适合分类为亚种。RB 50和Tohama I的高度基因型和表型相关性有利于对发病机制的比较研究，它们在BALB/c小鼠的鼻、气管和肺中生长以及诱导细胞凋亡、肺病理和抗体应答的能力不同。为了关注细菌与宿主免疫反应特定方面之间的相互作用，我们使用了具有特定免疫缺陷的小鼠。缺乏B细胞和T细胞的小鼠对B高度易感。支气管败血症，并杀死鼻内接种剂量低至500 CFU。这些小鼠未被B杀死。百日咳，甚至当高达10（5）CFU的剂量被递送至肺时，B。支气管败血症，这是高度耐幼稚血清在体外，造成菌血症，在这些免疫缺陷小鼠，而B。对幼稚血清高度敏感的百日咳不引起菌血症。B。然而，支气管败血症在体外被免疫血清杀死，并且抗博德特氏菌抗体的过继转移保护了SCID-米色小鼠免受B感染。支气管败血症致死性感染中性粒细胞减少小鼠同样被B杀死。支气管败血症而不是B。百日咳感染，表明中性粒细胞是至关重要的早期炎症反应，前者，而不是后者。B。支气管败血症的活性明显高于B。百日咳杆菌在体外介导J774细胞裂解和诱导小鼠肺炎性细胞凋亡。这种并排比较描述了可能与这两种高度相关的生物体的基因组的比较分析中的遗传差异相关的表型差异。
We describe here a side-by-side comparison of murine respiratory infection by Bordetella pertussis and Bordetella bronchiseptica strains whose genomes are currently being sequenced (Tohama I and RB50, respectively). B. pertussis and B. bronchiseptica are most appropriately classified as subspecies. Their high degree of genotypic and phenotypic relatedness facilitates comparative studies of pathogenesis, RB50 and Tohama I differ in their abilities to grow in the nose, trachea, and lungs of BALB/c mice and to induce apoptosis, lung pathology, and an antibody response. To focus on the interactions between the bacteria and particular aspects of the host immune response, we used mice with specific immune defects. Mice lacking B cells and T cells were highly susceptible to B. bronchiseptica and were killed by intranasal inoculation with doses as low as 500 CFU. These mice were not killed by B. pertussis, even when doses as high as 10(5) CFU were delivered to the lungs, B. bronchiseptica, which was highly resistant to naive serum in vitro, caused bacteremia in these immunodeficient mice, while B. pertussis, which was highly sensitive to naive serum, did not cause bacteremia. B. bronchiseptica was, however, killed by immune serum in vitro, and adoptive transfer of anti;Bordetella antibodies protected SCID-beige mice from B. bronchiseptica lethal infection. Neutropenic mice were similarly killed by B. bronchiseptica but not B. pertussis infection, suggesting neutrophils are critical to the early inflammatory response to the former but not the latter. B. bronchiseptica was dramatically more active than B. pertussis in mediating the lysis of J774 cells in vitro and in inducing apoptosis of inflammatory cells in mouse lungs. This side-by-side comparison describes phenotypic differences that may be correlated with genetic differences in the comparative analysis of the genomes of these two highly related organisms.