BALB/c and C57Bl/6 mice infected with virulent Burkholderia pseudomallei provide contrasting animal models for the acute and chronic forms of human melioidosis

BALB/c and C57Bl/6 mice infected with virulent Burkholderia pseudomallei provide contrasting animal models for the acute and chronic forms of human melioidosis
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DOI:
10.1006/mpat.1997.0179
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发表时间:
1998-05-01
影响因子:
3.8
通讯作者:
Hirst, RG
Hirst, RG
中科院分区:
医学3区
文献类型:
--
作者:
Leakey, AK;Ulett, GC;Hirst, RG

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类鼻疽伯克霍尔德氏菌是类鼻疽的病原体,类鼻疽是一种危及生命的细菌性疾病,发生在包括人类在内的许多动物物种中。人类感染通常表现为三种临床表现之一:急性、亚急性或慢性疾病。进行研究以评估 BALB/c 和 C57Bl/6 小鼠作为不同形式的人类类鼻疽动物模型的适用性。 BALB/c小鼠的感染过程与人类急性感染相似。相比之下,C57Bl/6 小鼠的感染似乎模仿了人类慢性类鼻疽病。 BALB/c 小鼠出现快速进展的菌血症,导致宿主在 96 小时内死亡,而 C57Bl/6 小鼠能够预防这种情况,并且通常在长达 6 周内保持无症状。 BALB/c 和 C57Bl/6 小鼠的 4 个细胞和 2.5 x 10(4) 个细胞的 LD50 值分别反映了这些观察结果。当检查第一代和相互回交代的易感性时,表明在 C57Bl/6 小鼠中观察到的对类鼻疽伯克氏菌的抗性水平升高具有遗传基础。检查 BALB/c 和 C57Bl/6 腹膜渗出细胞 (PEC) 培养物中拟鼻疽伯克氏菌的生长动力学,以研究 PEC 杀菌效率作为宿主敏感性的决定因素。与 BALB/c 细胞相比,C57Bl/6 PEC 培养物对拟鼻疽伯克氏菌表现出更高的杀菌效率,表明敏感性可能是由非特异性细胞机制决定的。总的来说,这些结果表明 BALB/c 和 C57Bl/6 品系小鼠可能分别为急性和慢性人类类鼻疽病提供优异的模型。 (C) 1998 学术出版社有限公司。
Burkholderia pseudomallei is the aetiological agent of melioidosis, a life-threatening bacterial disease occurring in many species of animals, including man. Infection in humans commonly manifests as one of three clinical presentations: acute, subacute or chronic disease. Investigations were undertaken to assess the suitability of BALB/c and C57Bl/6 mice as animal models for the different forms of human melioidosis. The course of infection in BALB/c mice was similar to that which occurs in acute human infection. By contrast, infection of C57Bl/6 mice appeared to mimic chronic human melioidosis. While BALB/c mice suffered a rapidly-progressive bacteraemia which resulted in host death by 96 h, C57Bl/6 mice were able to prevent this, and typically remained asymptomatic for up to 6 weeks. LD50 values of 4 cells and 2.5 x 10(4) cells for BALB/c and C57Bl/6 mice, respectively, reflect these observations, The heightened level of resistance to B. pseudomallei observed in C57Bl/6 mice was suggested to have a genetic basis, when the susceptibilities of first filial and reciprocal backcross generations were examined. Growth kinetics of B. pseudomallei within BALB/c and C57Bl/6 peritoneal exudate cell (PEC) cultures were examined to investigate PEC microbicidal efficiency as a determinant of host susceptibility C57Bl/6 PEC cultures exhibited greater microbicidal efficiency towards B. pseudomallei when compared to BALB/c cells, indicating that susceptibility may be determined by non-specific, cellular mechanisms. Collectively, these results suggest that the BALB/c and C57Bl/6 strains of mice may provide excellent models for acute and chronic human melioidosis, respectively. (C) 1998 Academic Press Limited.