This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hutchison, M. L.
Right arrow Articles by Govan, J. R. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hutchison, M. L.
Right arrow Articles by Govan, J. R. W.

 Previous Article  |  Next Article 

Infect Immun, May 1998, p. 2033-2039, Vol. 66, No. 5
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Burkholderia cepacia Produces a Hemolysin That Is Capable of Inducing Apoptosis and Degranulation of Mammalian Phagocytes

Michael L. Hutchison,* Ian R. Poxton, and John R. W. Govan

Department of Medical Microbiology, University of Edinburgh Medical School, Edinburgh EH8 9AG, Scotland

Received 9 June 1997/Returned for modification 3 September 1997/Accepted 28 January 1998

Burkholderia cepacia is an opportunistic pathogen that has become a major threat to individuals with cystic fibrosis (CF). In approximately 20% of patients, pulmonary colonization with B. cepacia leads to cepacia 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 characterized a factor which contributes to this hemolytic activity and is secreted from B. cepacia J2315, a representative of the virulent and highly transmissible strain belonging to the recently described genomovar III grouping. Biochemical data from the described purification method for this hemolysin allows us to hypothesize that the toxin is a lipopeptide. As demonstrated for other lipopeptide toxins, the hemolysin 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 concentrations of the hemolysin were able to induce nucleosomal degradation consistent with apoptosis in human neutrophils and the mouse-derived 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 the results obtained in this study, we suggest a role that allows B. cepacia to thwart the immune response and a model of the events that may contribute to the severe inflammatory response in the lungs of CF patients.

* Corresponding author. Mailing address: Department of Medical Microbiology, University of Edinburgh Medical School, Teviot Place, Edinburgh EH8 9AG, Scotland. Phone: (44) 131 6503165. Fax: (44) 131 6506531. E-mail: Mikeh{at}srv1.med.ed.ac.uk.

Infect Immun, May 1998, p. 2033-2039, Vol. 66, No. 5
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Saldias, M. S., Valvano, M. A. (2009). Interactions of Burkholderia cenocepacia and other Burkholderia cepacia complex bacteria with epithelial and phagocytic cells. Microbiology 155: 2809-2817 [Abstract] [Full Text]  
  • Boussaud, V, Guillemain, R, Grenet, D, Coley, N, Souilamas, R, Bonnette, P, Stern, M (2008). Clinical outcome following lung transplantation in patients with cystic fibrosis colonised with Burkholderia cepacia complex: results from two French centres. Thorax 63: 732-737 [Abstract] [Full Text]  
  • Aubert, D. F., Flannagan, R. S., Valvano, M. A. (2008). A Novel Sensor Kinase-Response Regulator Hybrid Controls Biofilm Formation and Type VI Secretion System Activity in Burkholderia cenocepacia. Infect. Immun. 76: 1979-1991 [Abstract] [Full Text]  
  • Bianchi, S. M., Prince, L. R., McPhillips, K., Allen, L., Marriott, H. M., Taylor, G. W., Hellewell, P. G., Sabroe, I., Dockrell, D. H., Henson, P. W., Whyte, M. K. B. (2008). Impairment of Apoptotic Cell Engulfment by Pyocyanin, a Toxic Metabolite of Pseudomonas aeruginosa. Am. J. Respir. Crit. Care Med. 177: 35-43 [Abstract] [Full Text]  
  • Chung, J. W., Speert, D. P. (2007). Proteomic identification and characterization of bacterial factors associated with Burkholderia cenocepacia survival in a murine host. Microbiology 153: 206-214 [Abstract] [Full Text]  
  • Kooi, C., Subsin, B., Chen, R., Pohorelic, B., Sokol, P. A. (2006). Burkholderia cenocepacia ZmpB Is a Broad-Specificity Zinc Metalloprotease Involved in Virulence. Infect. Immun. 74: 4083-4093 [Abstract] [Full Text]  
  • Whitby, P. W., VanWagoner, T. M., Springer, J. M., Morton, D. J., Seale, T. W., Stull, T. L. (2006). Burkholderia cenocepacia utilizes ferritin as an iron source. J Med Microbiol 55: 661-668 [Abstract] [Full Text]  
  • Desnues, B., Ihrig, M., Raoult, D., Mege, J.-L. (2006). Whipple's Disease: a Macrophage Disease. CVI 13: 170-178 [Full Text]  
  • Watt, A P, Courtney, J, Moore, J, Ennis, M, Elborn, J S (2005). Neutrophil cell death, activation and bacterial infection in cystic fibrosis. Thorax 60: 659-664 [Abstract] [Full Text]  
  • Bylund, J., Campsall, P. A., Ma, R. C., Conway, B.-A. D., Speert, D. P. (2005). Burkholderia cenocepacia Induces Neutrophil Necrosis in Chronic Granulomatous Disease. J. Immunol. 174: 3562-3569 [Abstract] [Full Text]  
  • Ortega, X., Hunt, T. A., Loutet, S., Vinion-Dubiel, A. D., Datta, A., Choudhury, B., Goldberg, J. B., Carlson, R., Valvano, M. A. (2005). Reconstitution of O-Specific Lipopolysaccharide Expression in Burkholderia cenocepacia Strain J2315, Which Is Associated with Transmissible Infections in Patients with Cystic Fibrosis. J. Bacteriol. 187: 1324-1333 [Abstract] [Full Text]  
  • Huber, B., Feldmann, F., Kothe, M., Vandamme, P., Wopperer, J., Riedel, K., Eberl, L. (2004). Identification of a Novel Virulence Factor in Burkholderia cenocepacia H111 Required for Efficient Slow Killing of Caenorhabditis elegans. Infect. Immun. 72: 7220-7230 [Abstract] [Full Text]  
  • Chu, K. K., MacDonald, K. L., Davidson, D. J., Speert, D. P. (2004). Persistence of Burkholderia multivorans within the Pulmonary Macrophage in the Murine Lung. Infect. Immun. 72: 6142-6147 [Abstract] [Full Text]  
  • Engledow, A. S., Medrano, E. G., Mahenthiralingam, E., LiPuma, J. J., Gonzalez, C. F. (2004). Involvement of a Plasmid-Encoded Type IV Secretion System in the Plant Tissue Watersoaking Phenotype of Burkholderia cenocepacia. J. Bacteriol. 186: 6015-6024 [Abstract] [Full Text]  
  • Hunt, T. A., Kooi, C., Sokol, P. A., Valvano, M. A. (2004). Identification of Burkholderia cenocepacia Genes Required for Bacterial Survival In Vivo. Infect. Immun. 72: 4010-4022 [Abstract] [Full Text]  
  • De Soyza, A., Ellis, C. D., Khan, C. M. A., Corris, P. A., de Hormaeche, R. D. (2004). Burkholderia cenocepacia Lipopolysaccharide, Lipid A, and Proinflammatory Activity. Am. J. Respir. Crit. Care Med. 170: 70-77 [Abstract] [Full Text]  
  • Jia, J., Alaoui-El-Azher, M., Chow, M., Chambers, T. C., Baker, H., Jin, S. (2003). c-Jun NH2-Terminal Kinase-Mediated Signaling Is Essential for Pseudomonas aeruginosa ExoS-Induced Apoptosis. Infect. Immun. 71: 3361-3370 [Abstract] [Full Text]  
  • Punj, V., Sharma, R., Zaborina, O., Chakrabarty, A. M. (2003). Energy-Generating Enzymes of Burkholderia cepacia and Their Interactions with Macrophages. J. Bacteriol. 185: 3167-3178 [Abstract] [Full Text]  
  • Neumeister, B., Faigle, M., Lauber, K., Northoff, H., Wesselborg, S. (2002). Legionella pneumophila induces apoptosis via the mitochondrial death pathway. Microbiology 148: 3639-3650 [Abstract] [Full Text]  
  • CANT, A.J., GORDON, S.B., READ, R.C., HART, C.A., WINSTANLEY, C. (2002). Respiratory infections: Proceedings of the Eighth Liverpool Tropical School Bayer Symposium of Microbial Disease held on 3 February 2001. J Med Microbiol 51: 903-914 [Full Text]  
  • Chu, K. K., Davidson, D. J., Halsey, T. K., Chung, J. W., Speert, D. P. (2002). Differential Persistence among Genomovars of the Burkholderia cepacia Complex in a Murine Model of Pulmonary Infection. Infect. Immun. 70: 2715-2720 [Abstract] [Full Text]  
  • Cieri, M. V., Mayer-Hamblett, N., Griffith, A., Burns, J. L. (2002). Correlation between an In Vitro Invasion Assay and a Murine Model of Burkholderia cepacia Lung Infection. Infect. Immun. 70: 1081-1086 [Abstract] [Full Text]  
  • Usher, L. R., Lawson, R. A., Geary, I., Taylor, C. J., Bingle, C. D., Taylor, G. W., Whyte, M. K. B. (2002). Induction of Neutrophil Apoptosis by the Pseudomonas aeruginosa Exotoxin Pyocyanin: A Potential Mechanism of Persistent Infection. J. Immunol. 168: 1861-1868 [Abstract] [Full Text]  
  • Huber, B., Riedel, K., Hentzer, M., Heydorn, A., Gotschlich, A., Givskov, M., Molin, S., Eberl, L. (2001). The cep quorum-sensing system of Burkholderia cepacia H111 controls biofilm formation and swarming motility. Microbiology 147: 2517-2528 [Abstract] [Full Text]  
  • Sajjan, U., Thanassoulis, G., Cherapanov, V., Lu, A., Sjolin, C., Steer, B., Wu, Y. J., Rotstein, O. D., Kent, G., McKerlie, C., Forstner, J., Downey, G. P. (2001). Enhanced Susceptibility to Pulmonary Infection with Burkholderia cepacia in Cftr{-}/{-} Mice. Infect. Immun. 69: 5138-5150 [Abstract] [Full Text]  
  • SAJJAN, U., COREY, M., HUMAR, A., TULLIS, E., CUTZ, E., ACKERLEY, C., FORSTNER, J. (2001). Immunolocalisation of Burkholderia cepacia in the lungs of cystic fibrosis patients. J Med Microbiol 50: 535-546 [Abstract] [Full Text]  
  • Lowe, C. A., Asghar, A. H., Shalom, G., Shaw, J. G., Thomas, M. S. (2001). The Burkholderia cepacia fur gene: co-localization with omlA and absence of regulation by iron. Microbiology 147: 1303-1314 [Abstract] [Full Text]  
  • Berriatua, E., Ziluaga, I., Miguel-Virto, C., Uribarren, P., Juste, R., Laevens, S., Vandamme, P., Govan, J. R. W. (2001). Outbreak of Subclinical Mastitis in a Flock of Dairy Sheep Associated with Burkholderia cepacia Complex Infection. J. Clin. Microbiol. 39: 990-994 [Abstract] [Full Text]  
  • SAJJAN, U., WU, Y., KENT, G., FORSTNER, J. (2000). Preferential adherence of cable-piliated Burkholderia cepacia to respiratory epithelia of CF knockout mice and human cystic fibrosis lung explants. J Med Microbiol 49: 875-885 [Abstract] [Full Text]  
  • Arakawa, S., Nakajima, T., Ishikura, H., Ichinose, S., Ishikawa, I., Tsuchida, N. (2000). Novel Apoptosis-Inducing Activity in Bacteroides forsythus: a Comparative Study with Three Serotypes of Actinobacillus actinomycetemcomitans. Infect. Immun. 68: 4611-4615 [Abstract] [Full Text]  
  • Behnia, M., Robertson, K. A., Martin, W. J. II (2000). Lung Infections : Role of Apoptosis in Host Defense and Pathogenesis of Disease. Chest 117: 1771-1777 [Abstract] [Full Text]  
  • Sajjan, U. S., Sylvester, F. A., Forstner, J. F. (2000). Cable-Piliated Burkholderia cepacia Binds to Cytokeratin 13 of Epithelial Cells. Infect. Immun. 68: 1787-1795 [Abstract] [Full Text]  
  • Mahenthiralingam, E., Coenye, T., Chung, J. W., Speert, D. P., Govan, J. R. W., Taylor, P., Vandamme, P. (2000). Diagnostically and Experimentally Useful Panel of Strains from the Burkholderia cepacia Complex. J. Clin. Microbiol. 38: 910-913 [Abstract] [Full Text]  
  • Martin, D. W., Mohr, C. D. (2000). Invasion and Intracellular Survival of Burkholderia cepacia. Infect. Immun. 68: 24-29 [Abstract] [Full Text]  
  • Saini, L. S., Galsworthy, S. B., John, M. A., Valvano, M. A. (1999). Intracellular survival of Burkholderia cepacia complex isolates in the presence of macrophage cell activation. Microbiology 145: 3465-3475 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»