BURKHOLDERIA CEPACIA PRODUCES A HEMOLYSIN THAT IS CAPABLE OF INDUCINGAPOPTOSIS AND DEGRANULATION OF MAMMALIAN PHAGOCYTES

Burkholderia cepacia is an opportunistic pathogen that has become a ma jor threat to individuals with cystic fibrosis (CF), In approximately 20% of patients, pulmonary colonization with B. cepacia leads to cepac ia syndrome, a fatal fulminating pneumonia sometimes associated: with septicemia. It has been reported that culture filtrates of clinically derived strains of B. cepacia are hemolytic, In this study, we have ch aracterized a factor which contributes to this hemolytic activity and is secreted from B. cepacia J2315, a representative of the virulent an d highly transmissible strain belonging to the recently described geno movar III grouping. Biochemical data from the described purification m ethod for this hemolysin allows us to hypothesize that the toxin is a lipopeptide, As demonstrated for other lipopeptide toxins, the hemolys in from B. cepacia was surface active and lowered the surface tension of high-pressure liquid chromatography-grade water from 72.96 to 29.8 mN m(-1). Similar to reports for other pore-forming cytotoxins, low co ncentrations of the hemolysin were able to induce nucleosomal degradat ion consistent with apoptosis in human neutrophils and the mouse-deriv ed macrophage-type cell line J774.2. Exposure of human neutrophils to higher concentrations of toxin resulted in increased activities of the neutrophil degranulation markers cathepsin G and elastase, Based on t he results obtained in this study, we suggest a role that allows B. ce pacia to thwart the immune response and a model of the events that may contribute to the severe inflammatory response in the lungs of CF pat ients.