The Fim and FhaB adhesins play a crucial role in nasal cavity infection and Bordetella pertussis transmission in a novel mouse catarrhal infection model.
The Fim and FhaB adhesins play a crucial role in nasal cavity infection and Bordetella pertussis transmission in a novel mouse catarrhal infection model.
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DOI：
10.1371/journal.ppat.1010402
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发表时间：
2022-04
期刊：
影响因子：
6.7
通讯作者：
中科院分区：
文献类型：
--
作者：
百日咳杆菌引起的肺部感染曾经是前疫苗时代婴儿死亡的主要原因，百日咳肺炎的小鼠模型用于表征B。百日咳毒力机制然而，生物学上最相关的卡他性疾病阶段和B。由于人类适应的病原体在鼠鼻咽粘膜上的增殖有限，因此百日咳传播在成年小鼠中没有充分再现。我们使用免疫缺陷的C57 BL/6 J MyD 88 KO小鼠来实现B。百日咳增殖至每个鼻腔108个活细菌的类人高计数，以引起鼻窦炎，伴随着B的强烈脱落和传播。百日咳菌群对成年共同圈养的MyD 88 KO小鼠的影响。实验用的是一套全面的B。百日咳毒素、腺苷酸环化酶毒素-溶血素、T3 SS效应子BteA/BopC等几种已知的毒力因子与鼻腔感染和B有关。百日咳在免疫受损MyD 88 KO小鼠中的传播。相比之下，缺乏丝状血凝素（FhaB）或菌毛（Fim）粘附素的突变体感染鼻腔较差，以低水平脱落，未能有效感染共同饲养的MyD 88 KO或C57 BL/6 J小鼠。因此，Fha B和菌毛似乎在B中起关键作用。百日咳传播。本文描述的新型小鼠B模型。百日咳引起的鼻卡他为B相关宿主机制的遗传学解剖开辟了道路。本研究旨在确定未来百日咳疫苗应针对的关键细菌传播因素。百日咳是一种严格意义上的人类呼吸道传染病，对幼儿和老年人可能是致命的。目前使用的脑内或肺B.百日咳感染在B型的鉴定中起着非常好的作用。百日咳毒力因子和有效百日咳疫苗的开发。然而，B。由于人类病原体在小鼠上呼吸道中的增殖有限，因此百日咳传播不能在成年小鼠中再现。因此，我们接种免疫缺陷MyD 88基因敲除小鼠的鼻腔，以实现类似人类的高水平鼻粘膜感染。这允许触发鼻炎和卡他性细菌从小鼠鼻腔脱落，并将感染有效传播到共同饲养的成年动物中。测试一组细菌突变体，我们确定了两个细菌粘附素作为关键的传播因子。结合小鼠和细菌遗传学的力量，这种新建立的百日咳卡他性阶段小鼠模型将使解释B的机制成为可能。百日咳传播到新的宿主。
Pulmonary infections caused by Bordetella pertussis used to be the prime cause of infant mortality in the pre-vaccine era and mouse models of pertussis pneumonia served in characterization of B. pertussis virulence mechanisms. However, the biologically most relevant catarrhal disease stage and B. pertussis transmission has not been adequately reproduced in adult mice due to limited proliferation of the human-adapted pathogen on murine nasopharyngeal mucosa. We used immunodeficient C57BL/6J MyD88 KO mice to achieve B. pertussis proliferation to human-like high counts of 108 viable bacteria per nasal cavity to elicit rhinosinusitis accompanied by robust shedding and transmission of B. pertussis bacteria to adult co-housed MyD88 KO mice. Experiments with a comprehensive set of B. pertussis mutants revealed that pertussis toxin, adenylate cyclase toxin-hemolysin, the T3SS effector BteA/BopC and several other known virulence factors were dispensable for nasal cavity infection and B. pertussis transmission in the immunocompromised MyD88 KO mice. In contrast, mutants lacking the filamentous hemagglutinin (FhaB) or fimbriae (Fim) adhesins infected the nasal cavity poorly, shed at low levels and failed to productively infect co-housed MyD88 KO or C57BL/6J mice. FhaB and fimbriae thus appear to play a critical role in B. pertussis transmission. The here-described novel murine model of B. pertussis-induced nasal catarrh opens the way to genetic dissection of host mechanisms involved in B. pertussis shedding and to validation of key bacterial transmission factors that ought to be targeted by future pertussis vaccines. Pertussis is a strictly human respiratory infectious disease that can be fatal to young children and elderly. The currently used mouse models of intracerebral or pulmonary B. pertussis infection served remarkably well in identification of B. pertussis virulence factors and development of efficacious pertussis vaccines. However, B. pertussis transmission could not be reproduced in adult mice due to limited proliferation of the human pathogen in the upper airways of mice. Therefore, we inoculated nasal cavities of immunodeficient MyD88 knock-out mice to achieve a human-like high level of nasal mucosa infection. This allowed triggering of rhinitis and catarrhal shedding of bacteria from mouse nasal cavity and efficient transmission of the infection onto co-housed adult animals. Testing a set of bacterial mutants, we identified two bacterial adhesins as key transmission factors. Combined with the power of mouse and bacterial genetics, this newly established mouse model of the catarrhal phase of the whooping cough disease will enable deciphering of mechanisms that underlie B. pertussis transmission to new hosts.
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影响因子：
3.4
作者：
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