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伯克霍尔德菌进入呼吸道上皮:CFTR、微丝和微管的依赖性。

Entry of Burkholderia organisms into respiratory epithelium: CFTR, microfilament and microtubule dependence.

机构信息

Division of Allergy, Immunology and Pulmonary Medicine, Department of Pediatrics, St. Louis Children's Hospital, Washington University School of Medicine, St. Louis, Missouri 63110, USA.

出版信息

J Cyst Fibros. 2010 Jan;9(1):36-43. doi: 10.1016/j.jcf.2009.10.002. Epub 2009 Nov 14.

Abstract

BACKGROUND

The pathogenesis of infection with Burkholderia cepacia complex (Bcc) organisms may be linked to its capacity to invade respiratory epithelium.

METHODS

An antibiotic exclusion assay was used to study B. dolosa AU4459 and B. cenocepacia J2315 invasion into wild-type (WT) and CFTR-deficient respiratory epithelial cells. Inhibitors were used to evaluate Bcc invasion dependency on host microtubule (mt) and microfilament (mf) systems.

RESULTS

B. dolosa entered WT-CFTR cells with 5-fold greater efficiency than CFTR deficient cells (25% vs 5%, respectively). Invasion dropped to <0.5% after either mf or mt inhibition. B. cenocepacia entered WT (0.05%) and CFTR-deficient cells (0.07%) with similarly low efficiencies, which significantly decreased with either mf or mt inhibition (0.008% and 0.002%, respectively).

CONCLUSION

B. dolosa and B. cenocepacia enter respiratory epithelial cells in a mf and mt dependent fashion. Mutated CFTR leads to less internalization of B. dolosa, but not B. cenocepacia.

摘要

背景

洋葱伯克霍尔德菌复合群(Bcc)感染的发病机制可能与其侵袭呼吸道上皮的能力有关。

方法

采用抗生素排除法研究了 D 型洋葱伯克霍尔德菌 AU4459 和 J2315 侵袭野生型(WT)和 CFTR 缺陷型呼吸道上皮细胞的能力。使用抑制剂评估了 Bcc 侵袭对宿主微管(mt)和微丝(mf)系统的依赖性。

结果

D 型洋葱伯克霍尔德菌进入 WT-CFTR 细胞的效率比 CFTR 缺陷细胞高 5 倍(分别为 25%和 5%)。mf 或 mt 抑制后,侵袭率降至<0.5%。B. cenocepacia 进入 WT(0.05%)和 CFTR 缺陷细胞(0.07%)的效率相似,mf 或 mt 抑制后显著降低(分别为 0.008%和 0.002%)。

结论

D 型和 C 型洋葱伯克霍尔德菌以 mf 和 mt 依赖的方式进入呼吸道上皮细胞。突变型 CFTR 导致 D 型洋葱伯克霍尔德菌内化减少,但对 C 型洋葱伯克霍尔德菌没有影响。

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