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Correlation between an In Vitro Invasion Assay and a Murine Model of Burkholderia cepacia Lung Infection

机译:洋葱伯克霍尔德氏菌肺感染的体外侵袭试验与小鼠模型之间的相关性

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Our understanding of the virulence of Burkholderia cepacia complex lung infections in cystic fibrosis patients is incomplete. There is a great deal of variability in the clinical course, from simple colonization to severe and often fatal necrotizing pneumonia, termed cepacia syndrome. Multiple subspecies (called genomovars) have been identified, and these genomovars may hold the key to understanding the variable pathogenicity. Thirty-one B. cepacia complex isolates belonging to five of the seven genomovars were examined by using a gentamicin protection assay of invasion with A549 cells. The level of epithelial cell invasion by B. cepacia in the A549 model was relatively low compared with the data obtained for other pathogens and was often variable from assay to assay. Thus, a statistical approach was used to determine invasiveness. When this model was used, one of four genomovar I strains (25%), three of eight genomovar II strains (37.5%), seven of nine genomovar III strains (77.8%), one of four genomovar IV strains (25%), and none of the four genomovar V strains examined were defined as invasive. All other strains were categorized as either noninvasive or indeterminate. Invasive, noninvasive, and indeterminate isolates belonging to genomovars II and III were subsequently tested for splenic invasion with the mouse agar bead model. Correlation between the models for six strains was demonstrated. Our results indicate that a statistical model used to determine invasiveness in an in vitro invasion assay can be used to predict in vivo invasiveness.
机译:我们对囊性纤维化患者 Burkholderia cepacia 复杂肺部感染的毒性了解不完整。从简单的定植到严重的,经常致命的坏死性肺炎(称为酒糟综合征),临床过程中存在很大的可变性。已经鉴定出多个亚种(称为基因型),这些基因型可能是理解可变致病性的关键。三十一个B.采用庆大霉素对A549细胞侵袭的保护作用,检测了属于七个基因组中的五个的复杂的洋葱分离物。 B侵袭上皮细胞的水平。与从其他病原体获得的数据相比,A549模型中的洋葱减少程度相对较低,并且在不同的检测方法之间经常存在差异。因此,使用统计方法确定侵袭性。使用此模型时,四个genomovar I菌株之一(25%),八个genomovar II菌株3个(37.5%),九个genomovar III菌株7个(77.8%),四个genomovar IV菌株之一(25%),且所检查的四个基因型V菌株均未定义为侵袭性的。所有其他菌株均分类为无创或不确定的。随后使用小鼠琼脂珠模型对属于基因突变型II和III的有创,无创和不确定的分离株进行了脾侵袭测试。证明了六个菌株的模型之间的相关性。我们的结果表明,用于确定体外侵袭试验中侵袭性的统计模型可用于预测体内侵袭性。

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