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在暴露于低剂量雾化临床分离的伯克霍尔德菌假单胞菌的小鼠中疾病的进展。

Disease progression in mice exposed to low-doses of aerosolized clinical isolates of Burkholderia pseudomallei.

机构信息

Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD, United States of America.

Pathology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD, United States of America.

出版信息

PLoS One. 2018 Nov 30;13(11):e0208277. doi: 10.1371/journal.pone.0208277. eCollection 2018.

DOI:10.1371/journal.pone.0208277
PMID:30500862
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6267979/
Abstract

Mouse models have been essential to generate supporting data for the research of infectious diseases. Burkholderia pseudomallei, the etiological agent of melioidosis, has been studied using mouse models to investigate pathogenesis and efficacy of novel medical countermeasures to include both vaccines and therapeutics. Previous characterization of mouse models of melioidosis have demonstrated that BALB/c mice present with an acute infection, whereas C57BL/6 mice have shown a tendency to be more resistant to infection and may model chronic disease. In this study, either BALB/c or C57BL/6 mice were exposed to aerosolized human clinical isolates of B. pseudomallei. The bacterial strains included HBPUB10134a (virulent isolate from Thailand), MSHR5855 (virulent isolate from Australia), and 1106a (relatively attenuated isolate from Thailand). The LD50 values were calculated and serial sample collections were performed in order to examine the bacterial burdens in tissues, histopathological features of disease, and the immune response mounted by the mice after exposure to aerosolized B. pseudomallei. These data will be important when utilizing these models for testing novel medical countermeasures. Additionally, by comparing highly virulent strains with attenuated isolates, we hope to better understand the complex disease pathogenesis associated with this bacterium.

摘要

小鼠模型对于生成传染病研究的支持数据至关重要。类鼻疽伯克霍尔德菌是类鼻疽病的病原体,已通过小鼠模型进行研究,以调查新型医疗对策(包括疫苗和疗法)的发病机制和疗效。先前对类鼻疽小鼠模型的特征描述表明,BALB/c 小鼠呈现出急性感染,而 C57BL/6 小鼠则表现出对感染的抵抗力增强,可能模拟慢性疾病。在这项研究中,BALB/c 或 C57BL/6 小鼠暴露于雾化的人类临床类鼻疽伯克霍尔德菌分离株。细菌株包括 HBPUB10134a(来自泰国的毒力分离株)、MSHR5855(来自澳大利亚的毒力分离株)和 1106a(来自泰国的相对减毒分离株)。计算了 LD50 值,并进行了连续样本采集,以检查组织中的细菌负荷、疾病的组织病理学特征以及暴露于雾化类鼻疽伯克霍尔德菌后小鼠的免疫反应。在利用这些模型测试新型医疗对策时,这些数据将非常重要。此外,通过比较高毒力菌株与减毒分离株,我们希望更好地了解与该细菌相关的复杂疾病发病机制。

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