Correlation between an in vitro invasion assay and a murine model of Burkholderia cepacia lung infection

Correlation between an in vitro invasion assay and a murine model of Burkholderia cepacia lung infection
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DOI:
10.1128/iai.70.3.1081-1086.2002
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发表时间:
2002-03-01
影响因子:
3.1
通讯作者:
Burns, JL
Burns, JL
中科院分区:
医学2区
文献类型:
--
作者:
Cieri, MV;Mayer-Hamblett, N;Burns, JL

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我们对洋葱伯克霍尔德菌复合体肺部感染对囊性纤维化患者的毒力的了解并不完整。临床病程存在很大差异,从简单的定植到严重且常常致命的坏死性肺炎(称为洋葱综合征)。多个亚种(称为基因变型)已被鉴定,这些基因变型可能是理解可变致病性的关键。通过使用 A549 细胞侵袭的庆大霉素保护测定,检查了属于七个基因变种中的五个的三十一个洋葱伯克霍尔德杆菌复合分离株。与其他病原体获得的数据相比,A549 模型中洋葱伯克霍尔德氏菌侵入上皮细胞的水平相对较低,并且在不同的测定中常常存在差异。因此,使用统计方法来确定侵袭性。使用该模型时,四种基因变种 I 菌株中的一种(25%)、八种基因变种 II 菌株中的三种(37.5%)、九种基因变种 III 菌株中的七种(77.8%)、四种基因变种 IV 菌株中的一种(25%)以及所检查的四种基因变种 V 菌株中没有一种被定义为侵入性。所有其他菌株都被归类为非侵入性或不确定性。随后用小鼠琼脂珠模型测试了属于基因变型 II 和 III 的侵袭性、非侵袭性和不确定分离株的脾侵袭情况。证明了六种菌株模型之间的相关性。我们的结果表明,用于确定体外侵袭测定中的侵袭性的统计模型可用于预测体内侵袭性。
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.