Difference in Virulence of Mycobacterium avium Isolates Sharing Indistinguishable DNA Fingerprint Determined in Murine Model of Lung Infection

Difference in Virulence of Mycobacterium avium Isolates Sharing Indistinguishable DNA Fingerprint Determined in Murine Model of Lung Infection
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DOI:
10.1371/journal.pone.0021673
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发表时间:
2011-06-28
期刊:
影响因子:
3.7
通讯作者:
Lasunskaia, Elena B.
Lasunskaia, Elena B.
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Amaral, Eduardo Pinheiro;Kipnis, Thereza Liberman;Lasunskaia, Elena B.

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背景资料:寄生性鸟分枝杆菌通常在免疫功能低下的患者和某些明显健康的个体群体中引起疾病。一些细菌谱系的高毒力增加了疾病的风险。高分辨率分子分型研究M.禽肺炎支原体临床分离株表明,一些基因型模式比其他人更普遍,这表明这些成功的分离株共享一个类似的基因型的密切遗传相关性可以确定类似的生物学特性与高vitrification.Methods和Findings:在这项研究中,我们的目的是比较两个流行病学无关的M.禽流感分离株共享一个不可区分的DNA指纹在一个良好的表征模型的肺部感染的小鼠,耐药或易感分枝杆菌。分别用两种分离株H27(人血液分离株)和P104(猪淋巴结分离株)对C57 BL/6野生型或IFN-γ基因破坏(GKO)小鼠进行气管内感染,并检查肺部的细菌负荷、组织病理学和细胞因子基因表达。所获得的数据表明,这些菌株的毒力特性的显着差异。虽然H27菌株在感染早期的生长速度明显快于P104,但这种细菌诱导了保护性免疫,开始减少野生型小鼠中的细菌数量,而P104菌株则建立了慢性感染。在GKO小鼠中,两种菌株都能够引起慢性感染,与较高的细菌负荷和严重的肺部病理学,以类似的方式.Conclusions/Significance:结果表明,所研究的分离株不同的致病特性,虽然是不可区分的,实际上广泛使用的基因分型技术表明,基因型相似性并不能预测相似的毒力M。禽流感分离株。
Background: Opportunistic Mycobacterium avium typically causes disease in immunocompromised patients and in some groups of apparently healthy individuals. The high virulence of some bacterial lineages increases the disease risk. High-resolution molecular genotyping studies of M. avium clinical isolates demonstrated that some genotype patterns were more prevalent than others, suggesting that close genetic relatedness of these successful isolates sharing a similar genotype could determine similar biological properties associated with high virulence.Methods and Findings: In this study, we aimed to compare the virulence and pathogenic properties of two epidemiologically unrelated M. avium isolates sharing an indistinguishable DNA fingerprint in a well-characterized model of pulmonary infection in mice, resistant or susceptible to mycobacteria. The mice, C57BL/6 wild-type or IFN-gamma gene disrupted (GKO), respectively, were intratracheally infected with two isolates, H27 (human blood isolate) and P104 (pig lymph node isolate), and the lungs were examined for bacterial loads, histopathology and cytokine gene expression. The obtained data demonstrated significant differences in the virulence properties of these strains. Although the H27 strain grew significantly faster than P104 in the early stage of infection, this bacterium induced protective immunity that started to reduce bacterial numbers in the wild-type mice, whereas the P104 strain established a chronic infection. In the GKO mice, both strains were capable of causing a chronic infection, associated with higher bacterial burdens and severe lung pathology, in a similar manner.Conclusions/Significance: The results demonstrated that the studied isolates differed in the pathogenic properties although were indistinguishable by actually widely used genotyping techniques demonstrating that the genotype similarity does not predict similarity in virulence of M. avium isolates.