Use of a Safe, Reproducible, and Rapid Aerosol Delivery Method to Study Infection by Burkholderia pseudomallei and Burkholderia mallei in Mice
Use of a Safe, Reproducible, and Rapid Aerosol Delivery Method to Study Infection by Burkholderia pseudomallei and Burkholderia mallei in Mice
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DOI：
10.1371/journal.pone.0076804
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发表时间：
2013-10-02
期刊：
影响因子：
3.7
通讯作者：
Hogan, Robert J.
中科院分区：
文献类型：
--
作者：
Lafontaine, Eric R.;Zimmerman, Shawn M.;Hogan, Robert J.
类鼻疽伯克霍尔德菌是类鼻疽的病原体，是一种容易从赤道附近国家的潮湿土壤中分离出来的腐殖菌。鼻疽伯克霍尔德菌是B的宿主适应性克隆。假鼻疽在马宿主之外不存在，并引起人畜共患病鼻疽，这是亚洲、非洲、中东和南美洲的地方病。这些微生物的感染通常通过经皮接种或吸入气溶胶发生，最常见的表现是导致致命菌血症的严重肺炎。腺体和类鼻疽很难诊断，需要长期的抗生素治疗，成功率低。目前还没有疫苗可以预防这两种伯克霍尔德氏菌，考虑到B.锤骨以前已经以这种方式使用。因此，进行实验以建立气溶胶感染的小鼠模型，以研究生物体并制定对策。使用手持式雾化器，用菌株B对BALB/c小鼠进行气管内接种。类鼻疽1026 B和B。检查鼻疽ATCC 23344的感染和肺中制剂的生长以及向脾的传播。感染10（2）、10（3）和10（4）微生物的小鼠不能控制B的生长。肺部出现鼻疽，细菌迅速传播到脾脏。尽管在接种10（3）和10（4）B的小鼠中观察到类似的结果。假鼻疽细胞，感染10（2）种微生物的动物控制了肺中的细菌复制、向脾的传播和菌血症的程度。对急性感染后存活的小鼠血清的分析表明，动物产生了针对已知是人类免疫反应靶点的抗原的抗体。总之，这些数据表明，小鼠的小体积气溶胶接种导致急性疾病、剂量依赖性慢性感染和与人类感染中观察到的免疫应答相关的免疫应答。
Burkholderia pseudomallei, the etiologic agent of melioidosis, is a saprophytic bacterium readily isolated from wet soils of countries bordering the equator. Burkholderia mallei is a host-adapted clone of B. pseudomallei that does not persist outside of its equine reservoir and causes the zoonosis glanders, which is endemic in Asia, Africa, the Middle East and South America. Infection by these organisms typically occurs via percutaneous inoculation or inhalation of aerosols, and the most common manifestation is severe pneumonia leading to fatal bacteremia. Glanders and melioidosis are difficult to diagnose and require prolonged antibiotic therapy with low success rates. There are no vaccines available to protect against either Burkholderia species, and there is concern regarding their use as biological warfare agents given that B. mallei has previously been utilized in this manner. Hence, experiments were performed to establish a mouse model of aerosol infection to study the organisms and develop countermeasures. Using a hand-held aerosolizer, BALB/c mice were inoculated intratracheally with strains B. pseudomallei 1026b and B. mallei ATCC23344 and growth of the agents in the lungs, as well as dissemination to the spleen, were examined. Mice infected with 10(2), 10(3) and 10(4) organisms were unable to control growth of B. mallei in the lungs and bacteria rapidly disseminated to the spleen. Though similar results were observed in mice inoculated with 10(3) and 10(4) B. pseudomallei cells, animals infected with 10(2) organisms controlled bacterial replication in the lungs, dissemination to the spleen, and the extent of bacteremia. Analysis of sera from mice surviving acute infection revealed that animals produced antibodies against antigens known to be targets of the immune response in humans. Taken together, these data show that small volume aerosol inoculation of mice results in acute disease, dose-dependent chronic infection, and immune responses that correlate with those seen in human infections.