J. Exp. Med.
© The Rockefeller University Press
0022-1007/97/10/1159/05 $2.00
Volume 186, Number 7, October 6, 1997 1159-1163

BRIEF DEFINITIVE REPORT:
pH-dependent Perforation of Macrophage Phagosomes by Listeriolysin O from Listeria monocytogenes

By Kathryn E. Beauregard,^* Kyung-Dall Lee,^* R. John Collier, and Joel A. Swanson^*

From the ^* Department of Cell Biology and  Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115

The pore-forming toxin listeriolysin O (LLO) is a major virulence factor implicated in escape of Listeria monocytogenes from phagocytic vacuoles. Here we describe the pH-dependence of vacuolar perforation by LLO, using the membrane-impermeant fluorophore 8-hydroxypyrene-1,3,6-trisulfonic acid (HPTS) to monitor the pH and integrity of vacuoles in mouse bone marrow-derived macrophages. Perforation was observed when acidic vacuoles containing wild-type L. monocytogenes displayed sudden increases in pH and release of HPTS into the cytosol. These changes were not seen with LLO-deficient mutants. Perforation occurred at acidic vacuolar pH (4.9-6.7) and was reduced in frequency or prevented completely when macrophages were treated with the lysosomotropic agents ammonium chloride or bafilomycin A₁. We conclude that acidic pH facilitates LLO activity in vivo.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Carrero, J. A., Vivanco-Cid, H., Unanue, E. R. (2008). Granzymes Drive a Rapid Listeriolysin O-Induced T Cell Apoptosis. J. Immunol. 181: 1365-1374 [Abstract] [Full Text]  
• Santic, M., Asare, R., Skrobonja, I., Jones, S., Abu Kwaik, Y. (2008). Acquisition of the Vacuolar ATPase Proton Pump and Phagosome Acidification Are Essential for Escape of Francisella tularensis into the Macrophage Cytosol. Infect. Immun. 76: 2671-2677 [Abstract] [Full Text]  
• Nitcheu-Tefit, J., Dai, M.-S., Critchley-Thorne, R. J., Ramirez-Jimenez, F., Xu, M., Conchon, S., Ferry, N., Stauss, H. J., Vassaux, G. (2007). Listeriolysin O Expressed in a Bacterial Vaccine Suppresses CD4+CD25high Regulatory T Cell Function In Vivo. J. Immunol. 179: 1532-1541 [Abstract] [Full Text]  
• Nomura, T., Kawamura, I., Kohda, C., Baba, H., Ito, Y., Kimoto, T., Watanabe, I., Mitsuyama, M. (2007). Irreversible loss of membrane-binding activity of Listeria-derived cytolysins in non-acidic conditions: a distinct difference from allied cytolysins produced by other Gram-positive bacteria. Microbiology 153: 2250-2258 [Abstract] [Full Text]  
• Yeung, P. S. M., Na, Y., Kreuder, A. J., Marquis, H. (2007). Compartmentalization of the Broad-Range Phospholipase C Activity to the Spreading Vacuole Is Critical for Listeria monocytogenes Virulence. Infect. Immun. 75: 44-51 [Abstract] [Full Text]  
• D'Orazio, S. E. F., Troese, M. J., Starnbach, M. N. (2006). Cytosolic Localization of Listeria monocytogenes Triggers an Early IFN-{gamma} Response by CD8+ T Cells That Correlates with Innate Resistance to Infection. J. Immunol. 177: 7146-7154 [Abstract] [Full Text]  
• Gray, M. J., Freitag, N. E., Boor, K. J. (2006). How the Bacterial Pathogen Listeria monocytogenes Mediates the Switch from Environmental Dr. Jekyll to Pathogenic Mr. Hyde.. Infect. Immun. 74: 2505-2512 [Full Text]  
• Jarry, T. M., Cheung, A. L. (2006). Staphylococcus aureus Escapes More Efficiently from the Phagosome of a Cystic Fibrosis Bronchial Epithelial Cell Line than from Its Normal Counterpart.. Infect. Immun. 74: 2568-2577 [Abstract] [Full Text]  
• Cerro-Vadillo, E. d., Madrazo-Toca, F., Carrasco-Marin, E., Fernandez-Prieto, L., Beck, C., Leyva-Cobian, F., Saftig, P., Alvarez-Dominguez, C. (2006). Cutting Edge: A Novel Nonoxidative Phagosomal Mechanism Exerted by Cathepsin-D Controls Listeria monocytogenes Intracellular Growth. J. Immunol. 176: 1321-1325 [Abstract] [Full Text]  
• Joseph, B., Przybilla, K., Stuhler, C., Schauer, K., Slaghuis, J., Fuchs, T. M., Goebel, W. (2006). Identification of Listeria monocytogenes Genes Contributing to Intracellular Replication by Expression Profiling and Mutant Screening. J. Bacteriol. 188: 556-568 [Abstract] [Full Text]  
• Tweten, R. K. (2005). Cholesterol-Dependent Cytolysins, a Family of Versatile Pore-Forming Toxins. Infect. Immun. 73: 6199-6209 [Full Text]  
• Cheng, L. W., Viala, J. P. M., Stuurman, N., Wiedemann, U., Vale, R. D., Portnoy, D. A. (2005). Use of RNA interference in Drosophila S2 cells to identify host pathways controlling compartmentalization of an intracellular pathogen. Proc. Natl. Acad. Sci. USA 102: 13646-13651 [Abstract] [Full Text]  
• Schuerch, D. W., Wilson-Kubalek, E. M., Tweten, R. K. (2005). Molecular basis of listeriolysin O pH dependence. Proc. Natl. Acad. Sci. USA 102: 12537-12542 [Abstract] [Full Text]  
• Agaisse, H., Burrack, L. S., Philips, J. A., Rubin, E. J., Perrimon, N., Higgins, D. E. (2005). Genome-Wide RNAi Screen for Host Factors Required for Intracellular Bacterial Infection. Science 309: 1248-1251 [Abstract] [Full Text]  
• Poussin, M. A., Goldfine, H. (2005). Involvement of Listeria monocytogenes Phosphatidylinositol-Specific Phospholipase C and Host Protein Kinase C in Permeabilization of the Macrophage Phagosome. Infect. Immun. 73: 4410-4413 [Abstract] [Full Text]  
• Andrade, L. O., Andrews, N. W. (2004). Lysosomal Fusion Is Essential for the Retention of Trypanosoma cruzi Inside Host Cells. J. Exp. Med. 200: 1135-1143 [Abstract] [Full Text]  
• Roy, D., Liston, D. R., Idone, V. J., Di, A., Nelson, D. J., Pujol, C., Bliska, J. B., Chakrabarti, S., Andrews, N. W. (2004). A Process for Controlling Intracellular Bacterial Infections Induced by Membrane Injury. Science 304: 1515-1518 [Abstract] [Full Text]  
• Rea, R. B., Gahan, C. G. M., Hill, C. (2004). Disruption of Putative Regulatory Loci in Listeria monocytogenes Demonstrates a Significant Role for Fur and PerR in Virulence. Infect. Immun. 72: 717-727 [Abstract] [Full Text]  
• Myers, J. T., Tsang, A. W., Swanson, J. A. (2003). Localized Reactive Oxygen and Nitrogen Intermediates Inhibit Escape of Listeria monocytogenes from Vacuoles in Activated Macrophages. J. Immunol. 171: 5447-5453 [Abstract] [Full Text]  
• Provoda, C. J., Stier, E. M., Lee, K.-D. (2003). Tumor Cell Killing Enabled by Listeriolysin O-liposome-mediated Delivery of the Protein Toxin Gelonin. J. Biol. Chem. 278: 35102-35108 [Abstract] [Full Text]  
• Cotter, P. D., Hill, C. (2003). Surviving the Acid Test: Responses of Gram-Positive Bacteria to Low pH. Microbiol. Mol. Biol. Rev. 67: 429-453 [Abstract] [Full Text]  
• Liu, S., Leppla, S. H. (2003). Cell Surface Tumor Endothelium Marker 8 Cytoplasmic Tail-independent Anthrax Toxin Binding, Proteolytic Processing, Oligomer Formation, and Internalization. J. Biol. Chem. 278: 5227-5234 [Abstract] [Full Text]  
• Portnoy, D. A., Auerbuch, V., Glomski, I. J. (2002). The cell biology of Listeria monocytogenes infection: the intersection of bacterial pathogenesis and cell-mediated immunity. J. Cell Biol. 158: 409-414 [Abstract] [Full Text]  
• Conte, M. P., Petrone, G., Di Biase, A. M., Longhi, C., Penta, M., Tinari, A., Superti, F., Fabozzi, G., Visca, P., Seganti, L. (2002). Effect of Acid Adaptation on the Fate of Listeria monocytogenes in THP-1 Human Macrophages Activated by Gamma Interferon. Infect. Immun. 70: 4369-4378 [Abstract] [Full Text]  
• Dramsi, S., Cossart, P. (2002). Listeriolysin O: a genuine cytolysin optimized for an intracellular parasite. J. Cell Biol. 156: 943-946 [Abstract] [Full Text]  
• Glomski, I. J., Gedde, M. M., Tsang, A. W., Swanson, J. A., Portnoy, D. A. (2002). The Listeria monocytogenes hemolysin has an acidic pH optimum to compartmentalize activity and prevent damage to infected host cells. J. Cell Biol. 156: 1029-1038 [Abstract] [Full Text]  
• Christensen, K. A., Myers, J. T., Swanson, J. A. (2002). pH-dependent regulation of lysosomal calcium in macrophages. J. Cell Sci. 115: 599-607 [Abstract] [Full Text]  
• Gaillot, O., Bregenholt, S., Jaubert, F., Di Santo, J. P., Berche, P. (2001). Stress-Induced ClpP Serine Protease of Listeria monocytogenes Is Essential for Induction of Listeriolysin O-Dependent Protective Immunity. Infect. Immun. 69: 4938-4943 [Abstract] [Full Text]  
• Wilson, R. L., Tvinnereim, A. R., Jones, B. D., Harty, J. T. (2001). Identification of Listeria monocytogenes In Vivo-Induced Genes by Fluorescence-Activated Cell Sorting. Infect. Immun. 69: 5016-5024 [Abstract] [Full Text]  
• Vazquez-Boland, J. A., Kuhn, M., Berche, P., Chakraborty, T., Dominguez-Bernal, G., Goebel, W., Gonzalez-Zorn, B., Wehland, J., Kreft, J. (2001). Listeria Pathogenesis and Molecular Virulence Determinants. Clin. Microbiol. Rev. 14: 584-640 [Abstract] [Full Text]  
• Gahan, C. G. M., O'Mahony, J., Hill, C. (2001). Characterization of the groESL Operon in Listeria monocytogenes: Utilization of Two Reporter Systems (gfp and hly) for Evaluating In Vivo Expression. Infect. Immun. 69: 3924-3932 [Abstract] [Full Text]  
• Ishiguro, T., Naito, M., Yamamoto, T., Hasegawa, G., Gejyo, F., Mitsuyama, M., Suzuki, H., Kodama, T. (2001). Role of Macrophage Scavenger Receptors in Response to Listeria monocytogenes Infection in Mice. Am. J. Pathol. 158: 179-188 [Abstract] [Full Text]  
• Sturgill-Koszycki, S., Swanson, M. S. (2000). Legionella pneumophila Replication Vacuoles Mature into Acidic, Endocytic Organelles. J. Exp. Med. 192: 1261-1272 [Abstract] [Full Text]  
• Tsang, A. W., Oestergaard, K., Myers, J. T., Swanson, J. A. (2000). Altered membrane trafficking in activated bone marrow-derived macrophages. J. Leukoc. Biol. 68: 487-494 [Abstract] [Full Text]  
• Browne, K. A., Blink, E., Sutton, V. R., Froelich, C. J., Jans, D. A., Trapani, J. A. (1999). Cytosolic Delivery of Granzyme B by Bacterial Toxins: Evidence that Endosomal Disruption, in Addition to Transmembrane Pore Formation, Is an Important Function of Perforin. Mol. Cell. Biol. 19: 8604-8615 [Abstract] [Full Text]  
• Zwickey, H. L., Potter, T. A. (1999). Antigen Secreted from Noncytosolic Listeria monocytogenes Is Processed by the Classical MHC Class I Processing Pathway. J. Immunol. 162: 6341-6350 [Abstract] [Full Text]  
• Ouadrhiri, Y., Scorneaux, B., Sibille, Y., Tulkens, P. M. (1999). Mechanism of the Intracellular Killing and Modulation of Antibiotic Susceptibility of Listeria monocytogenes in THP-1 Macrophages Activated by Gamma Interferon. Antimicrob. Agents Chemother. 43: 1242-1251 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS