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Journal of Clinical Microbiology, August 2005, p. 3956-3962, Vol. 43, No. 8
0095-1137/05/$08.00+0     doi:10.1128/JCM.43.8.3956-3962.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Early Immune Response to the Components of the Type III System of Pseudomonas aeruginosa in Children with Cystic Fibrosis

R. Corech,1 A. Rao,2 A. Laxova,3 J. Moss,4 M. J. Rock,3 Z. Li,5 M. R. Kosorok,5 M. L. Splaingard,2 P. M. Farrell,3 and J. T. Barbieri1*

Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, Wisconsin,1 Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin,2 Department of Pediatrics, University of Wisconsin Medical School, Madison, Wisconsin,3 Pulmonary Critical Care Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland,4 Department of Biostatistics and Medical Informatics, University of Wisconsin Medical School, Madison, Wisconsin5

Received 25 November 2004/ Returned for modification 5 January 2005/ Accepted 13 April 2005

The lungs of patients with cystic fibrosis (CF) are colonized initially by Pseudomonas aeruginosa, which is associated with progressive lung destruction and increased mortality. The pathogenicity of P. aeruginosa is caused by a number of virulence factors, including exotoxin A (ETA) and the type III cytotoxins (ExoS, ExoT, ExoU, and ExoY). P. aeruginosa contacts the plasma membrane to deliver type III cytotoxins through a channel formed by PopB, PopD, and PcrV; ETA enters mammalian cells via receptor-mediated endocytosis. The Wisconsin CF Neonatal Screening Project is a longitudinal investigation to assess the potential benefits and risks of newborn screening for CF; the project was the source of serum samples used in this study. Past studies evaluated the longitudinal appearance of antibodies to ETA and elastase and P. aeruginosa infections in patients with CF. The current study characterized the longitudinal appearance of antibodies to components of the type III system in children with CF. Western blot analyses showed that serum antibodies to PopB, PcrV, and ExoS were common. Longitudinal enzyme-linked immunosorbent assays determined that the first detection of antibodies to pooled ExoS/PopB occurred at a time similar to those of detection of antibodies to a P. aeruginosa cell lysate and the identification of oropharyngeal cultures positive for P. aeruginosa. This indicates that children with CF are colonized early with P. aeruginosa expressing the type III system, implicating it in early pathogenesis, and implies that surveillance of clinical symptoms, oropharyngeal cultures, and seroconversion to type III antigens may facilitate early detection of P. aeruginosa infections.

* Corresponding author. Mailing address: Medical College of Wisconsin, Microbiology and Molecular Genetics, 8701 Watertown Plank Road, Milwaukee, WI 53226. Phone: (414) 456-8412. E-mail: jtb01{at}mcw.edu.

Journal of Clinical Microbiology, August 2005, p. 3956-3962, Vol. 43, No. 8
0095-1137/05/$08.00+0     doi:10.1128/JCM.43.8.3956-3962.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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