Characterization of Coxiella burnetii Dugway Strain Host-Pathogen Interactions In Vivo.

Characterization of Coxiella burnetii Dugway Strain Host-Pathogen Interactions In Vivo.
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DOI:
10.3390/microorganisms10112261
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发表时间:
2022-11-15
期刊:
影响因子:
4.5
通讯作者:
Long CM
Long CM
中科院分区:
生物学3区
文献类型:
--
作者:
Tesfamariam M;Binette P;Cockrell D;Beare PA;Heinzen RA;Shaia C;Long CM

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伯氏柯克斯体是一种革兰氏阴性细胞内细菌,可引起人畜共患病Q热。在从各种来源回收的众多自然分离株中,Dugway群表现出独特的遗传特征,包括最大的伯氏弧菌基因组。这些菌株是1954-1958年间从美国犹他州沙漠中的野生啮齿动物中分离到的。尽管保留了I相脂多糖和4B型分泌系统这两个关键的毒力因子,但在豚鼠感染模型中已报道了无毒。利用豚鼠模型,我们评估了具有代表性的Dugway毒株的毒力、全细胞疫苗(WCV)效力和接种后超敏反应(PVH)潜力。与之前的报道一致,与毒力株相比,Dugway似乎具有高度的减毒作用。事实上,感染Dugway的动物表现出与Nine Mile II感染的动物一样的低发烧、体重减轻和脾肿大。与人类Q热疫苗QVax®相比,Dugway WCV对异源九里I挑战表现出类似的保护作用。在皮肤测试模型中对PVH进行了研究,发现与Δ®相比,Dugway QVAX Dot/ICM WCV皮试动物的最大红斑显著减少。这些数据提供了对这种独特的细菌菌株的洞察,并暗示其作为突变的WCV候选菌株的潜在用途。
Coxiella burnetii is a Gram-negative, intracellular bacterium that causes the zoonosis Q fever. Among the many natural isolates of C. burnetii recovered from various sources, the Dugway group exhibits unique genetic characteristics, including the largest C. burnetii genomes. These strains were isolated during 1954–1958 from wild rodents from the Utah, USA desert. Despite retaining phase I lipopolysaccharide and the type 4B secretion system, two critical virulence factors, avirulence has been reported in a guinea pig infection model. Using guinea pig models, we evaluated the virulence, whole-cell vaccine (WCV) efficacy, and post-vaccination hypersensitivity (PVH) potential of a representative Dugway strain. Consistent with prior reports, Dugway appeared to be highly attenuated compared to a virulent strain. Indeed, Dugway-infected animals showed similarly low levels of fever, body weight loss, and splenomegaly like Nine Mile II-infected animals. When compared to a human Q fever vaccine, QVax®, Dugway WCV exhibited analogous protection against a heterologous Nine Mile I challenge. PVH was investigated in a skin-testing model which revealed significantly decreased maximum erythema in Dugway Δdot/icm WCV-skin-tested animals compared to that of QVax®. These data provide insight into this unique bacterial strain and implicate its potential use as a mutated WCV candidate.
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影响因子: 9.2
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