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Infection and Immunity, August 2002, p. 4547-4555, Vol. 70, No. 8
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.8.4547-4555.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Patterns of Epithelial Cell Invasion by Different Species of the Burkholderia cepacia Complex in Well-Differentiated Human Airway Epithelia

Cystic Fibrosis/Pulmonary Research and Treatment Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7248,¹ Department of Microbiology and Infectious Diseases, University of Calgary Health Sciences Center, Calgary, Alberta, Canada T2N 4N1²

Received 25 February 2002/ Returned for modification 2 April 2002/ Accepted 8 May 2002

Burkholderia cepacia has emerged as a serious respiratory pathogen in cystic fibrosis (CF) patients. The clinical course of B. cepacia infections is variable, but 20% of patients eventually succumb to the cepacia syndrome, which is characterized as a fatal necrotizing pneumonia with bacteremia. The mechanisms that permit B. cepacia to cause bacteremia are not yet known but probably involve sequential penetration of airway barriers. This study evaluated the abilities of different species of the B. cepacia complex, including a strain from the ET12 lineage (BC-7, genomovar III, cblA⁺), which is associated with most cepacia syndrome fatalities among CF populations, a genomovar IV strain (HI2258), and a genomovar II strain (J-1) to penetrate polarized, well-differentiated human airway epithelial cell cultures. As revealed by light and electron microscopy, all three B. cepacia strains tested circumvented the mechanical barriers of mucus and ciliary transport to penetrate the airway epithelium but they used different routes. The BC-7 strain (genomovar III) formed biofilms in close proximity to the apical cell surface, followed by invasion and destruction of epithelial cells. This process involved disruption of the glycocalyx and rearrangements of the actin cytoskeleton. The HI2258 strain (genomovar IV) did not form biofilms, and the majority of bacteria that penetrated the epithelium were located between epithelial cells, suggesting paracytosis. Strain J-1 penetrated the epithelium both by cell destruction and paracytosis. These studies suggest that the distinct invasion pathways employed by B. cepacia may account for differences in virulence between B. cepacia genomovars.

Editor: D. L. Burns

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