Binding of Pseudomonas aeruginosa to respiratory epithelial cells from patients with various mutations in the cystic fibrosis transmembrane regulator

doi:10.1016/S0022-3476(95)70549-X

The Journal of Pediatrics

Volume 126, Issue 2, February 1995, Pages 230-233

https://doi.org/10.1016/S0022-3476(95)70549-X Get rights and content

Abstract

Objective: To determine whether there is an association between mutations of the cystic fibrosis transmembrane regulator (CFTR) and the predilection of patients with cystic fibrosis (CF) for Pseudomonas aeruginosa infection. Method: We quantified the adherence of P. aeruginosa PA01, labeled with sulfur 35-methionine, to epithelial monolayers derived from nasal scrapings of patients with specific CFTR mutations, and of carriers and normal subjects. Results: Adherence of P. aeruginosa to epithelial cells from patients with CF was significantly greater than to cells from either carriers (t = 2.94; p = 0.009) or normal subjects (t = 3.32; p = 0.004). Adherence to epithelial cells from patients with CF who were homozygous for the ΔF508 mutation ranged from 12% to 35% (mean, 23.7%) of the added inoculum, which was significantly greater than the binding to cells from patients with other mutations, which ranged from 3% to 18% (mean, 9.4%; t = 3.71; p = 0.002), from heterozygote carriers (3% to 11%; mean, 7.9%; t = 4.87; p = 0.002), or from normal subjects (2% to 10%: mean, 7.0%; t = 5.21; p = 0.002). Conclusion: Adherence to P. aeruginosa can be correlated with homozygosity for the &Drg;508 mutation; CFTR dysfunction may be one of the factors involved in the pathogenesis of pulmonary infection in CF. (J PEDIATR 1995;126:230-3)

Section snippets

Subjects

Nasal epithelial cells were obtained from 15 patients with CF, 15 normal subjects, and 10 parents of patients with CF (obligate heterozygotes). All patients with CF were colonized with P. aeruginosa as defined by positive results of sputum cultures for this organism for at least 6 months. The extent of pulmonary disease was evaluated with the Shwachman-Kulczycki scoring system. ⁹ All but one patient had evidence of pancreatic insufficiency and received replacement enzyme therapy. Normal

Patient population

The study patients with CF represented a diverse group in terms of both their genotypes and the extent of pulmonary disease (Table I). Within the group of seven patients homozygous for ΔF508 were four patients with mild disease (Shwachman-Kulczycki score >80) and three patients with moderate disease (Shwachman-Kulczycki score 50 to 80). The eight patients with ”other“ mutations included a 43-year-old, fully functional professional woman with moderate pulmonary disease and a 60-year-old man who

DISCUSSION

This study attempted to establish a relationship between CF genotype and P. aeruginosa infection by focusing on a single measurement relevant to the pathogenesis of infection, namely, the avidity of epithelial cells for P. aeruginosa binding. Our results indicate that P. aeruginosa PAO1 binds significantly more to the epithelial cells of patients homozygous for the &Drg;F508 mutation than to those of patients with other CF mutations, heterozygote carriers, or normal subjects. However, no

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^☆: From the Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, New York

^☆☆: Supported by U.S. Public Health Service grant DK36963 (Dr. Prince) and by the Cystic Fibrosis Foundation Research Development Program at Columbia University.

^★: Reprint requests: Alice Prince, MD, Pediatric Infectious Diseases, Columbia University, 650 W. 168th St., New York, NY 10032.

^★★: 0022-3476/95/$3.00 + 0 9/20/60006

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The Journal of Pediatrics

Abstract

Section snippets

Subjects

Patient population

DISCUSSION

References (15)

Prognostic implications of initial oropharyngeal bacterial flora in patients with cystic fibrosis diagnosed before the age of two years

J PEDIATR

Pulmonary function and clinical course in patients with cystic fibrosis after pulmonary colonization with Pseudomonas aeruginosa

J PEDIATR

Severity of cystic fibrosis in patients homozygous and heterozygous for ΔF508 mutation

Lancet

Genetic determinants of airways' colonization with Pseudomonas aeruginosa in cystic fibrosis

Lancet

Molecular mechanisms of CFTR chloride channel dysfunction in cystic fibrosis

Cell

Independent genetic determinants of pancreatic and pulmonary status in cystic fibrosis

Lancet

Genetic determinants of exocrine pancreatic function in cystic fibrosis

Am J Hum Genet

Cited by (92)

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Type IV pilus protein PilA of Pseudomonas aeruginosa modulates calcium signaling through binding the calcium-modulating cyclophilin ligand

Cystic Fibrosis

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Pathogenesis of Bronchiectasis

Exploring the mechanisms of macrolides in cystic fibrosis

Binding of Pseudomonas aeruginosa to respiratory epithelial cells from patients with various mutations in the cystic fibrosis transmembrane regulator☆,☆☆,★,★★

Abstract

Section snippets

Subjects

Patient population

DISCUSSION

J PEDIATR

J PEDIATR

Lancet

Lancet

Cell

Lancet

Genetic determinants of exocrine pancreatic function in cystic fibrosis

Am J Hum Genet