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.
