Pilus-mediated epithelial cell death in response to infection with Burkholderia cenocepacia

Burkholderia cenocepacia is an opportunistic pathogen that can cause serious infections in cystic fibrosis (CF) patients. The ET12 lineage appears particularly virulent in CF; however, its pathogenesis is poorly understood and may be associated with host response. To help characterize this response,...

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Bibliographic Details
Published in:Microbes and infection 2007-06, Vol.9 (7), p.829-837
Main Authors: Cheung, K-John, Li, Gang, Urban, Teresa A., Goldberg, Joanna B., Griffith, Adam, Lu, Fuqu, Burns, Jane L.
Format: Article
Language:English
Subjects:
Annexin A5 - chemistry
Apoptosis
Apoptosis - physiology
Bacteriology
Biological and medical sciences
Blotting, Western
Burkholderia
Burkholderia cenocepacia
Burkholderia cepacia complex - growth & development
Burkholderia cepacia complex - metabolism
Burkholderia cepacia complex - pathogenicity
Burkholderia Infections - microbiology
Burkholderia Infections - pathology
Caspases - metabolism
Cell Line
Cell Survival - physiology
Cystic fibrosis
Cystic Fibrosis - microbiology
Cystic Fibrosis - pathology
DNA Fragmentation
Epithelial Cells - metabolism
Epithelial Cells - pathology
Fimbriae, Bacterial - pathology
Flow Cytometry
Fundamental and applied biological sciences. Psychology
Human lung epithelial cell
Humans
Microbiology
Microscopy, Fluorescence
Miscellaneous
Propidium - chemistry
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Summary:Burkholderia cenocepacia is an opportunistic pathogen that can cause serious infections in cystic fibrosis (CF) patients. The ET12 lineage appears particularly virulent in CF; however, its pathogenesis is poorly understood and may be associated with host response. To help characterize this response, the ability of B. cenocepacia to induce cytotoxicity and apoptosis in an epithelial cell model was examined. Upon infection with B. cenocepacia strain K56-2, A549 human lung epithelial cells underwent significant cell death; propidium iodine staining and DNA fragmentation assays suggested apoptosis. Initiation of cell death was independent of the type III secretion system, biofilm formation, and secreted bacterial cytotoxins. However, the frequency of cell death was lower in cells infected with a non-piliated mutant, K56-2 cblA::Tp. Furthermore, purified cbl pili were found to directly induce cytotoxicity in A549 cells and activate caspase-9, -8, -7, and -3, the major cysteine proteinases involved in apoptosis. It appears that B. cenocepacia cbl pili, which are a distinctive feature of the ET12 lineage, act as an initiator of cytotoxicity and apoptosis. Understanding the role of cbl pili in the pathogenesis of B. cenocepacia infections offers the potential for decreasing the virulence of these potentially life-threatening organisms in CF patients.
ISSN:1286-4579
1769-714X
DOI:10.1016/j.micinf.2007.03.001