Escherichia coli hemolysin (Hly) is a proteinaceous pore-forming exotoxin that probably represents a significant virulence factor in E. coli infections. We investigated its influence on human polymorphonuclear neutrophils (PMN), previously identified as highly susceptible targets. Hly provoked rapid secretion of elastase and myeloperoxidase, generation of superoxide, and synthesis of platelet-activating factor (PAF) and lyso-PAF. Concomitantly, marked phosphatidylinositol (PtdIns) hydrolysis with sequential appearance of the inositol-phosphates, inositol-phosphates, inositol triphosphate, diphosphate, and monophosphate, respectively, and formation of diacylglycerol, occurred. The metabolic responses displayed distinct bell-shaped dose dependencies, with maximum events noted at low toxin concentrations of 0.1-0.5 hemolytic units per milliliter. PtdIns hydrolysis and metabolic responses elicited by Hly exceeded those evoked by optimal concentrations of formylmethionyl-leucyl phenylalanine, PAF, leukotriene B4, A23187, or staphylococcal alpha-toxin. The toxin-induced effects were sensitive toward modulators of PMN stimulus transmission pathways (pertussis toxin, the kinase C inhibitor H7, and phorbol myristate acetate "priming"). We conclude that the marked capacity of low doses of Hly to elicit degranulation, respiratory burst, and lipid mediator generation in human PMN probably envolves signal transduction via PtdIns hydrolysis.
F Grimminger, U Sibelius, S Bhakdi, N Suttorp, W Seeger
Title and authors | Publication | Year |
---|---|---|
Pathological analysis and antimicrobial susceptibility of Chryseobacterium balustinum RTFCP 298 isolated from diseased rainbow trout, Oncorhynchus mykiss.
Mallik SK, Pathak R, Shahi N, Kala K, Chandra S, Das P, Singh B, Singh M, Giri AK, Tandel RS, Sarma D, Pandey PK |
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Kingella kingae RtxA Cytotoxin in the Context of Other RTX Toxins.
Filipi K, Rahman WU, Osickova A, Osicka R |
Microorganisms | 2022 |
The bacteria and the host: a story of purinergic signaling in urinary tract infections
H Praetorius |
American journal of physiology. Cell physiology | 2021 |
Characterization of Flavobacterium columnare from farmed infected rainbow trout, Oncorhynchus mykiss (Walbaum, 1792) of Central Indian Himalayan region, India
S Singh, SK Mallik, K Kala, N Shahi, R Pathak, AK Giri, S Chandra, K Pant, RS Patiyal |
Aquaculture | 2021 |
The Extracellular Domain of the β 2 Integrin β Subunit (CD18) Is Sufficient for Escherichia coli Hemolysin and Aggregatibacter actinomycetemcomitans Leukotoxin Cytotoxic Activity
LC Ristow, V Tran, KJ Schwartz, L Pankratz, A Mehle, JD Sauer, RA Welch, VJ Torres |
mBio | 2019 |
Inhibition of P2X Receptors Protects Human Monocytes against Damage by Leukotoxin from Aggregatibacter actinomycetemcomitans and α-Hemolysin from Escherichia coli
SK Fagerberg, MR Jakobsen, M Skals, HA Praetorius, SR Blanke |
Infection and immunity | 2016 |
Hemolysin of Uropathogenic Escherichia coli: A Cloak or a Dagger?
LC Ristow, RA Welch |
Biochimica et Biophysica Acta (BBA) - Biomembranes | 2015 |
The RTX pore-forming toxin α-hemolysin of uropathogenic Escherichia coli : progress and perspectives
TJ Wiles, MA Mulvey |
Future Microbiology | 2013 |
Advances in Applied Microbiology
JL Brooks, KK Jefferson |
Advances in applied microbiology | 2012 |
Alpha Hemolysin Induces an Increase of Erythrocytes Calcium: A FLIM 2-Photon Phasor Analysis Approach
S Sanchez, L Bakás, E Gratton, V Herlax, D Holowka |
PloS one | 2011 |
Methods in Microbiology
V Tchikov, J Fritsch, D Kabelitz, S Schütze |
Methods in Microbiology | 2010 |
Inactivation of Host Akt/Protein Kinase B Signaling by Bacterial Pore-forming Toxins
TJ Wiles, BK Dhakal, DS Eto, MA Mulvey, J York |
Molecular biology of the cell | 2008 |
The multiple mechanisms of Ca2+ signalling by listeriolysin O, the cholesterol-dependent cytolysin of Listeria monocytogenes
NO Gekara, K Westphal, B Ma, M Rohde, L Groebe, S Weiss |
Cellular Microbiology | 2007 |
Pro-inflammatory feedback activation cycle evoked by attack of Vibrio cholerae cytolysin on human neutrophil granulocytes
A Valeva, I Walev, S Weis, F Boukhallouk, TM Wassenaar, S Bhakdi |
Medical Microbiology and Immunology | 2007 |
Sepsis
JM O’Brien, NA Ali, SK Aberegg, E Abraham |
The American Journal of Medicine | 2007 |
HlyA knock out yields a safer Escherichia coli A0 34/86 variant with unaffected colonization capacity in piglets
V Sheshko, J Hejnova, Z Rehakova, J Sinkora, M Faldyna, P Alexa, J Felsberg, R Nemcova, A Bomba, P Sebo |
FEMS Immunology and Medical Microbiology | 2006 |
The Comprehensive Sourcebook of Bacterial Protein Toxins
JD Dubreuil |
The Comprehensive Sourcebook of Bacterial Protein Toxins | 2006 |
Evolution of Microbial Pathogens
HS Seifert, VJ DiRita |
2006 | |
Binding of Escherichia coli Hemolysin and Activation of the Target Cells Is Not Receptor-dependent
A Valeva, I Walev, H Kemmer, S Weis, I Siegel, F Boukhallouk, TM Wassenaar, T Chavakis, S Bhakdi |
The Journal of biological chemistry | 2005 |
Hyperpermeability of pulmonary endothelial monolayer: Protective role of phosphodiesterase isoenzymes 3 and 4
N Suttorp, P Ehreiser, S Hippenstiel, M Fuhrmann, M Krll, H Tenor, C Schudt |
Lung | 2004 |
Leukotriene-mediated coronary vasoconstriction and loss of myocardial contractility evoked by low doses of Escherichia coli hemolysin in perfused rat hearts*
U Sibelius, U Grandel, M Buerke, L Kiss, P Klingenberger, M Heep, E Bournelis, W Seeger, F Grimminger |
Critical Care Medicine | 2003 |
Staphylococcal α-toxin synergistically enhances inflammation caused by bacterial components
T Onogawa |
FEMS Immunology & Medical Microbiology | 2002 |
Dual effects of Escherichia coliα-hemolysin on rat renal proximal tubule cells
Å Laestadius, A Richter-Dahlfors, A Aperia |
Kidney International | 2002 |
Increased frequency of intestinal Escherichia coli carrying genes for S fimbriae and haemolysin in IgA-deficient individuals
V Friman, F Nowrouzian, I Adlerberth, AE Wold |
Microbial Pathogenesis | 2002 |
Pore-Forming Toxins
FG van der Goot |
2001 | |
Initial Characterization of the Hemolysin Stachylysin from Stachybotrys chartarum
RN Moore, SJ Vesper, ML Magnuson, DG Dearborn, I Yike, RA Haugland |
Infection and immunity | 2001 |
E. coli hemolysin-induced lipid mediator metabolism in alveolar macrophages: impact of eicosapentaenoic acid
F Rose, L Kiss, F Grimminger, K Mayer, U Grandel, W Seeger, E Bieniek, U Sibelius |
American journal of physiology. Lung cellular and molecular physiology | 2000 |
Dangerous signals from E. coli toxin
A Ludwig, W Goebel |
Nature Medicine | 2000 |
Contribution of Escherichia coli Alpha-Hemolysin to Bacterial Virulence and to Intraperitoneal Alterations in Peritonitis
JT Barbieri, AK May, TG Gleason, RG Sawyer, TL Pruett |
Infection and immunity | 2000 |
Symposium in Immunology VIII
MM Eibl, C Huber, HH Peter, U Wahn |
1999 | |
Role of Listeria monocytogenes Exotoxins Listeriolysin and Phosphatidylinositol-Specific Phospholipase C in Activation of Human Neutrophils
DL Burns, U Sibelius, EC Schulz, F Rose, K Hattar, T Jacobs, S Weiss, T Chakraborty, W Seeger, F Grimminger |
Infection and immunity | 1999 |
Wegener's granulomatosis: anti-proteinase 3 antibodies are potent inductors of human endothelial cell signaling and leakage response
U Sibelius, K Hattar, A Schenkel, T Noll, E Csernok, WL Gross, WJ Mayet, HM Piper, W Seeger, F Grimminger |
Journal of Experimental Medicine | 1998 |
Wegener's Granulomatosis: Anti-proteinase 3 Antibodies Are Potent Inductors of Human Endothelial Cell Signaling and Leakage Response
U Sibelius, K Hattar, A Schenkel, T Noll, E Csernok, WL Gross, WJ Mayet, HM Piper, W Seeger, F Grimminger |
Journal of Experimental Medicine | 1998 |
Nitric Oxide Biosynthesis in an Exotoxin-induced Septic Lung Model: Role of cNOS and Impact on Pulmonary Hemodynamics
H Schütte, K Mayer, T Gessler, M Rühl, J Schlaudraff, H Burger, W Seeger, F Grimminger |
American journal of respiratory and critical care medicine | 1998 |
VEGF induces hyperpermeability by a direct action on endothelial cells
S Hippenstiel, M Krüll, A Ikemann, W Risau, M Clauss, N Suttorp |
American journal of physiology. Lung cellular and molecular physiology | 1998 |
Aerolysin Induces G-protein Activation and Ca 2+ Release from Intracellular Stores in Human Granulocytes
KH Krause, M Fivaz, A Monod, FG van der Goot |
The Journal of biological chemistry | 1998 |
Synergism Between Endotoxin Priming and Exotoxin Challenge in Provoking Severe Vascular Leakage in Rabbit Lungs
H Schütte, S Rosseau, R Czymek, L Ermert, D Walmrath, HJ Krämer, W Seeger, F Grimminger |
American journal of respiratory and critical care medicine | 1997 |
Listeriolysin is a potent inducer of the phosphatidylinositol response and lipid mediator generation in human endothelial cells
U Sibelius, F Rose, T Chakraborty, A Darji, J Wehland, S Weiss, W Seeger, F Grimminger |
Infection and immunity | 1996 |
Bacterial modulins: a novel class of virulence factors which cause host tissue pathology by inducing cytokine synthesis
B Henderson, S Poole, M Wilson |
Microbiological reviews | 1996 |
In vivo cytokine response to Escherichia coli alpha-hemolysin determined with genetically engineered hemolytic and nonhemolytic E. coli variants
AK May, RG Sawyer, T Gleason, A Whitworth, TL Pruett |
Infection and immunity | 1996 |
Association of RTX toxins with erythrocytes
ME Bauer, RA Welch |
Infection and immunity | 1996 |
Neutrophil activation by anti-proteinase 3 antibodies in Wegener's granulomatosis: role of exogenous arachidonic acid and leukotriene B4 generation
F Grimminger, K Hattar, C Papavassilis, B Temmesfeld, E Csernok, WL Gross, W Seeger, U Sibelius |
Journal of Experimental Medicine | 1996 |
Pore-forming toxins trigger shedding of receptors for interleukin 6 and lipopolysaccharide
I Walev, P Vollmer, M Palmer, S Bhakdi, S Rose-John |
Proceedings of the National Academy of Sciences | 1996 |
Molecular Mechanisms of Action of Bacterial Exotoxins
J Balfanz, P Rautenberg, U Ullmann |
Zentralblatt für Bakteriologie | 1996 |
Intensivtherapie bei Sepsis und Multiorganversagen
HP Schuster |
1996 | |
Pathology of Septic Shock
ET Rietschel, H Wagner |
1996 | |
Invited Review: Cell Damage in Inflammatory and Infectious Sites Might Involve A Coordinated “Cross-Talk” Among Oxidants, Microbial Haemolysins and Ampiphiles, Cationic Proteins, Phospholipases, Fatty Acids, Proteinases and Cytokines (An Overview)
I Ginsburg, R Kohen |
Free Radical Research | 1995 |
Characterization of the hemolytic activity of Haemophilus ducreyi
PA Totten, DV Norn, WE Stamm |
Infection and immunity | 1995 |
Pore formation by the Escherichia coli alpha-hemolysin: role for mediator release from human inflammatory cells
B König, A Ludwig, W Goebel, W König |
Infection and immunity | 1994 |
Endotoxin "priming" potentiates lung vascular abnormalities in response to Escherichia coli hemolysin: an example of synergism between endo- and exotoxin
D Walmrath, HA Ghofrani, S Rosseau, H Schütte, A Cramer, W Kaddus, F Grimminger, S Bhakdi, W Seeger |
Journal of Experimental Medicine | 1994 |
Gene targeting and generation of mutant mice for studies of cell-extracellular matrix interactions
KL Philpott, JL Viney, G Kay, S Rastan, EM Gardiner, S Chae, AC Hayday, MJ Owen |
Methods in enzymology | 1994 |
Molecular Genetics of Bacterial Pathogenesis: A Tribute to Stanley Falkow
VL Miller, JB Kaper, DA Portnoy, RR Isberg |
1994 | |
Proteinaceous bacterial toxins and pathogenesis of sepsis syndrome and septic shock: the unknown connection
S Bhakdi, F Grimminger, N Suttorp, D Walmrath, W Seeger |
Medical Microbiology and Immunology | 1994 |
Nanomolar arachidonic acid influences the respiratory burst in eosinophils and neutrophils induced by GTP-binding protein. A comparative study of the respiratory burst in bovine eosinophils and neutrophils
CP AEBISCHER, I PASCHE, A JORG |
European Journal of Biochemistry | 1993 |
Pathophysiology of Shock, Sepsis, and Organ Failure
G Schlag, H Redl |
1993 | |
In vivo effects of intravascularly applied Escherichia coli hemolysin: dissociation between induction of granulocytopenia and lethality in monkeys
D Vagts, HP Dienes, PJ Barth, H Ronneberger, KD Hungerer, S Bhakdi |
Medical Microbiology and Immunology | 1993 |
A guide to the use of pore-forming toxins for controlled permeabilization of cell membranes
S Bhakdi, U Weller, I Walev, E Martin, D Jonas, M Palmer |
Medical Microbiology and Immunology | 1993 |
A double-blind, randomized, placebo-controlled trial of n-3 fatty acid based lipid infusion in acute, extended guttate psoriasis: Rapid improvement of clinical manifestations and changes in neutrophil leukotriene profile
F Grimminger, P Mayser, C Papavassilis, M Thomas, E Schlotzer, KU Heuer, D Fhrer, KD Hinsch, D Walmrath, WB Schill, W Seeger |
The Clinical Investigator | 1993 |
The synthesis and function of theEscherichia colihemolysin and related RTX exotoxins
RA Welch, C Forestier, A Lobo, S Pellett, W Thomas, G Rowe |
FEMS Microbiology Letters | 1992 |