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囊性纤维化异种移植模型中呼吸道上皮的铜绿假单胞菌感染

Pseudomonas aeruginosa infection of respiratory epithelium in a cystic fibrosis xenograft model.

作者信息

Cohn L A, Weber A, Phillips T, Lory S, Kaplan M, Smith A

机构信息

Department of Veterinary Medicine and Surgery, University of Missouri-Columbia, Columbia, Missouri 65212, USA.

出版信息

J Infect Dis. 2001 Mar 15;183(6):919-27. doi: 10.1086/319245. Epub 2001 Feb 15.

Abstract

Pulmonary infection with Pseudomonas aeruginosa in patients with cystic fibrosis (CF) causes a chronic destructive bronchitis. A xenograft model was used to study the susceptibility of the CF respiratory epithelium to P. aeruginosa strain PAK and the virulence of certain mutants. Despite an early trend toward increased susceptibility, colonization of CF xenografts (ID(95), 62 colony-forming units [cfu]) was not statistically different (P=.5) than in xenografts with normal respiratory cells (ID(95), 1.2x10(3) cfu). Infection severity in 12 CF xenografts (mean polymorphonuclear leukocyte [PMNL] density, 1.88x10(6)+/-1.75x10(6)/xenograft) was similar to that in 16 non-CF xenografts (3.19x10(6)+/-2.45x10(6) PMNL/xenograft; P=.38), despite slightly greater bacterial density in the CF xenografts (mean, 1.57+/-2.73x10(6) cfu/xenograft) versus xenografts with normal epithelium (mean, 1.03+/-1.3x10(6) cfu/xenograft). P. aeruginosa mutants pilA and fliF, but not rpoN, colonized normal respiratory xenografts, indicating that colonization and infection in this model depend on an uncharacterized RpoN-controlled gene. This model appears to be suitable for genetic study of P. aeruginosa virulence but not of the CF respiratory tract's unique susceptibility.

摘要

囊性纤维化(CF)患者肺部感染铜绿假单胞菌会引发慢性破坏性支气管炎。采用异种移植模型研究CF呼吸道上皮细胞对铜绿假单胞菌PAK菌株的易感性以及某些突变体的毒力。尽管早期有易感性增加的趋势,但CF异种移植的定植(ID(95),62个菌落形成单位[cfu])与具有正常呼吸道细胞的异种移植(ID(95),1.2×10(3) cfu)相比,在统计学上并无差异(P = 0.5)。12个CF异种移植的感染严重程度(平均多形核白细胞[PMNL]密度,1.88×10(6)±1.75×10(6)/异种移植)与16个非CF异种移植(3.19×10(6)±2.45×10(6) PMNL/异种移植;P = 0.38)相似,尽管CF异种移植中的细菌密度(平均,1.57±2.73×10(6) cfu/异种移植)略高于具有正常上皮的异种移植(平均,1.03±1.3×10(6) cfu/异种移植)。铜绿假单胞菌突变体pilA和fliF,而非rpoN,能定植于正常呼吸道异种移植,这表明该模型中的定植和感染依赖于一个未明确的受RpoN控制的基因。此模型似乎适用于铜绿假单胞菌毒力的遗传学研究,但不适用于CF呼吸道独特易感性的研究。

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