Volume 5, Issue 3, September 2020, Page: 135-151
Staphylococcal Pore-forming Leukotoxins: Opening of Ca2+-activated K+ Channels and Specificity of Membrane Pores in Human Neutrophils
Leila Staali, Department of Biotechnology, Natural and Life Sciences Faculty, Ahmed Ben Bella Oran1-University, Oran, Algeria; Bacteriology Institute of Medical Faculty, Louis Pasteur University, Strasbourg, France
Didier Andre Colin, Bacteriology Institute of Medical Faculty, Louis Pasteur University, Strasbourg, France
Received: Jul. 14, 2020;       Accepted: Jul. 27, 2020;       Published: Aug. 20, 2020
DOI: 10.11648/j.ijmb.20200503.19      View  180      Downloads  65
Pore-forming toxins are key virulence determinants produced by human bacterial pathogens Staphylococcus aureus, inducing two independent cellular events in neutrophils. Upon a specific binding to membrane receptors, both Panton and Valentin Leukocidin and γ-hemolysin induced an increase of Na+ and K+ fluxes, likely associated to the activation of preexisting ionic channels or to the membrane pores formation. This was investigated by using, spectrofluorometry techniques and, specific molecular probes in human neutrophils. Interestingly, we found that, in the absence of extracellular Ca2+, leukotoxins did form membrane pores, which were large enough to allow a massive entry of ethidium into neutrophils. Simultaneously, sustained Na+ influx and K+ efflux were observed. Another set of experiments carried out in the presence of extracellular Ca2+ did show that, the percentage of pores formed by leukotoxins was significantly, reduced due to the Ca2+ effect to eventually protect cells from lysis. The simultaneous recording of Na+ and K+ movements showed a significant increase of the K+ efflux although, the Na+ influx was reduced. By using potassium channels blockers, we found that, the potassium efflux enhanced by the presence of extracellular Ca2+, was markedly, inhibited in apamin-, charybdotoxin-, tetrodotoxin-, and quinine-pretreatment neutrophils. We also found that, the increase of the K+ efflux was reduced by either, thapsigargin or TMB8, potent blockers of the internal Ca2+ stores depletion. Consequently, we proposed that, the activation of another potassium pathway by leukotoxins, known as Ca2+-activated K+ channels following the Ca2+ stores depletion. Furthermore, potassium channels blockers did not affect ethidium, Na+ and K+ movements, in the absence of extracellular Ca2+. Moreover, in this condition, no monovalent ions movement was recorded, when the pores formation was altered by tetra-ethyl-ammonium. In the present study, we further highlighted the specificity of membrane pores to Na+ and K+ ions when, the pores formation was completely blocked by divalent ions blockers (Ca2+ and Zn2+). Under these conditions, no monovalent ions movement, was recorded although, a significant influx of Ca2+ and Zn2+ was observed after the leukotoxins application. In conclusion, our data provided an evidence that, staphylococcal leukotoxins induced in human neutrophils: 1) the opening of Ca2+-activated K+ channels, only in the presence of 1 mM extracellular Ca2+; 2) the formation of membrane pores, which exhibited a high specificity to monovalent cations and, 3) an influx of sodium, through a tetrodotoxin not-sensitive pathway ruling out the hypothesis that, Na+ channels could be activated by leukotoxins.
Staphylococcal Pore-forming Leukotoxins: Opening of Ca2+-activated K+ Channels and Specificity of Membrane Pores in Human Neutrophils
To cite this article
Leila Staali, Didier Andre Colin, Staphylococcal Pore-forming Leukotoxins: Opening of Ca2+-activated K+ Channels and Specificity of Membrane Pores in Human Neutrophils, International Journal of Microbiology and Biotechnology. Vol. 5, No. 3, 2020, pp. 135-151. doi: 10.11648/j.ijmb.20200503.19
Copyright © 2020 Authors retain the copyright of this article.
This article is an open access article distributed under the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Vandenesch F, Lina G, Henry T (2012) Staphylococcus aureus hemolysins, bi-component leukocidins, and cytolytic peptides a redundant arsenal of membrane-damaging virulence factors? Front Cell Infect. Microbiol. 2: 12 (1-15).
Los FC, Randis TM, Aroian RV, Ratner AJ (2013) Role of pore-forming toxins in bacterial infectious diseases. Microbiol. Mol. Biol. Rev. 77: 173-207.
Yang Y, Hu Z, Shang W, Hu Q, Zhu J, Yang J, Peng H, Zhang X, Liu H, Cong Y, Li S, Hu X, Zhou R, Rao X (2017) Molecular and phenotypic characterization revealed high prevalence of multidrug-resistant methicillin-susceptible Staphylococcus aureus in Chongqing, South western China. Microb. Drug. Resist. 23: 241-246.
Dantes R, Mu Y, Belflower R, Aragon D, Dumyati G, Harrison LH, Lessa FC, Lynfield R, Nadle J, Petit S, Ray SM, Schaffner W, Townes J, Fridkin S, Emerging infections Program-Active bacterial Core Surveillance MSI (2013) National burden of invasive methicilin-resistant Staphylococcus aureus infections, United States, 2011. JAMA Intern Med 173: 1970-1978.
David MZ, Daum RS (2010) Community-associated methicillin-resistant Staphylococcus aureus: epidemiology and clinical consequences of an emerging epidemic. Clin. Microbiol. Rev. 23: 616-687.
Zhang X, Hu X, Rao X (2017) Apoptosis induced by Staphylococcus aureus toxins. Microbiological Research. 205: 19-24.
Finck-Barbançon V, Duportail G, Meunier O, Colin DA (1993) Pore formation by a two component leukocidin, from Staphylococcus aureus within the membrane of human polymorphonuclear leukocytes. Biochim. Biophys. Acta. 1128: 275-282.
Staali L, Monteil H, Colin DA (1998) The pore-forming leukotoxins from Staphylococcus aureus open Ca2+ channels in human polymorphonuclear neutrophils. J. Membr. Biol. 162: 209-216.
Bhakdi S, Tranum-Jensen J (1985) Membrane damage by channel-forming proteins: staphylococcal alpha toxin, stroptolysin-O and the C5b-9 complement complex. Biochem. Soc. Symp. 50: 221-233.
Menestrina G (1986) Ionic channels formed by Staphylococcus aureus alpha-toxin. J. Membr. Biol. 90: 177-190.
Alouf JE (1980) Streptococcal toxins (streptolysin O, streptolysin S, eryhtrogenic toxins) Pharmacol. Ther. 11: 661-717.
Scheffer J, Konig W, Braun V, Goebel W (1988) Comparison of four hemolysin-producing organisms (Escherichia coli, Serratia marcescens, Aeoromonas hydrophila, and Listeria monocytogenes) for release of inflammatory mediators from various cells. J. Clin. Microbiol. 26: 544-551.
Wilmsen HU, Pattus F, Buckley JT (1990) Aerolysin, a hemolysin from Aeromonas hydrophila, forms voltage-gated channels in planar lipid bilayers. J. Membr. Biol. 115 (1): 71-81.
Bouillot S, Reboud E, Huber P (2018) Functional consequences of calcium influx promoted by bacterial pore-forming toxins. Toxins 10: 387.
Staali L, Colin DA (2020) The pore-forming leukotoxins from S. aureus involve Ca2+-activated Ca2+ channels and other types of Ca2+ channels in Ca2+ entry into neutrophils. International Journal of Microbiology and Biotechnology. 5 (2): 55-68.
Staali L, Colin DA (2020) Bi-component staphylococcal leukotoxins induce chloride ions fluxes in human neutrophils: Opening of Ca2+-activated Cl- channels. International Journal of Microbiology and Biotechnology 5 (3): 110-119.
Simchowitz L, Spilberg I (1979) Chemotactic factor-induced generation of superoxide radicals by human neutrophils: evidence for the role of sodium. J. Immunol. 123 (5): 2428-2435.
Krautwurst D, Seifert R, Hescheler J, Schultz G (1992) Formyl peptides and ATP stimulate Ca2+ and Na+ inward currents through non-selective cation channels via G-proteins in dibutyryl cyclic AMP-differenciated HL-60 cells. Biochem. J. 288: 1025-1035.
Huffman DL, Abrami L, Sasik R, Corbeil J, Van der goot FG, Aroian RV (2004) Mitogen-activated protein kinase pathways defend against bacterial pore-forming toxins. Proc. Natl. Acad. Sci. USA 101 (30): 10995-11000.
Kloft N, Busch T, Neukirch C, Weis S, Boukhallouk F, Bobkiewicz W, Cibis I, Bhakdi S, Husmann M (2009) Pore-forming toxins activate MAPK p38 by causing loss of cellular potassium. Biochem. Biophys. Res. Commun. 385: 503-506.
Gonzalez MR, Bischofberger M, Freche B, Ho S, Parton RG, Van der Goot FG (2011) Pore-forming toxins induce multiple cellular responses promoting survival. Cell. Microbiol. 13: 1026-1043.
Munoz-Planillo R, Kuffa P, Martinez-Colon G, Smith BL, Rajendiran TM, Nunez G (2013) K+ efflux is the common trigger of NLRP3 inflammasome activation by bacterial toxins and particulate matter. Immunity 358 (6): 1142-1153.
Gonzalez-Juarbe N, Gilley RP, Hinojosa CA, Bradley KM, Kamei A, Gao G, Dube PH, Bergman MA, Orihuela CJ (2015) Pore-forming toxins induce macrophages necroptosis during acute bacterial pneumoniae. PloS One 9 (7): e99823.
Simchowitz L, Spilberg I, De Weer P (1982) Sodium and potassium fluxes and membrane potential of human neutrophils: evidence for an electrogenic sodium pump. J. Gen. Physiol. 79: 453-479.
Staali l, Monteil H, Colin DA (1998) Action mechanism of staphylococcal bi-component leucotoxins. Toxicon 36 (12): 1746.
Prévost G, Cribier B, Couppié P, Petiau P, Supersac G, Finck-Barbancon V, Monteil H, Piémont Y (1995) Panton-Valentine leucocidin and, gamma-hemolysin from Staphylococcus aureus ATCC49775 are encoded by distinct loci and, have different biological activities. Infect. Immun. 63: 4121-4129.
Amorino GP, Fox MH (1995) Intracellular Na+ measurements using sodium green tetra-acetate with flow cytometry. Cytometry 21: 248-256.
Kasner SE, Ganz MB (1992) Regulation of intracellular potassium in mesangial cells: a fluorescence analysis using the dye, PBFI. Am. J. physiol. 262: F462-467.
Krause K-H, Welsh MJ (1990) Voltage-dependent and Ca2+-activated ion channels in human neutrophils. J. Clin. Invest. 85: 491-498.
Krause K-H, Lew DP, Welsh MJ (1991) Electrophysiological properties of human neutrophils. Adv. Exp. Med. Biol. 297: 1-11.
Randriamampita C, Trautmann A (1987) Ionic channels in murine macrophages. J. Cell. Biol. 105: 761-769.
Anderson C, MacKinnon R, Smith C, Miller C (1988) Charybdotoxin block of single Ca2+-activated K+ channels. Effects of channel gating, voltage, ionic strength. J. Gen. Physiol. 91: 317-333.
Garcia ML, Galvez A, Garcia-Calvo M, King VF, Vazquez J, Kaczorowski GJ (1991) Use of toxins to study potassium channels. J. Bioenerg. Biomembr. 23: 615-646.
Wolff D, Cecchi X, Spalvins A, Canessa M (1988) Charybdotoxin blocks with high affinity the Ca2+-activated K+ channels of Hb A and Hb S red cells: Individual differences in the number of channels. J. Membr. Biol. 106: 243-252.
Romey G, Hugues M, Schmid-Antomarchi H, Lazdunski M (1984) Apamin: a specific toxin to study a class of Ca2+-depenent K+ channels. J. Physiol. 79 (4): 259-264.
Kerschbaum HH, Negulescu PA, Cahalan MD (1997) Ion channels, Ca2+ signaling, and reporter gene expression in antigen-specific mouse T cells. J. Immunol. 159: 1628-1638.
Thomson SH, Aldrich RW (1980) Membrane potassium channels. In the cell surface and Neuronal Function, ed. Cotman CW., Poste G.  Nicolson GL., pp 49-85. Amsterdam: Elseiver/North Hollan Biomedical Press.
Schwartz W, Passow H (1983) Ca2+-activated K+ channels in erythrocytes and excitable cells. Annual Review of Physiology 45: 359-374.
Nietsch HH, Roe MW, Fiekers JF, Moore AL, Lidofsky SD (2000) Activation of potassium and chloride channels by tumor necrosis factor-. The Journal of Biological Chemistry. 275 (27): 20556-20561.
Morgan AJ, Jacob R (1994) Ionomycin enhances Ca2+ influx by stimulating store-regulated cation entry and not by a direct action at the plasma membrane. Biochem. J. 300: 665-672.
Randriamampita C, Bismuth G, Trautmann A (1991) Ca2+-induced Ca2+ release amplifies the Ca2+ response elicited by inositol triphosphate in macrophages. Cell. Regul. 2: 513-522.
Sehgal P, Szalai P, Olesen C, Praetorius HA, Nissen P, Christensen SB, Engedal N, Mǿller JV (2017) Inhibition of the sarco/endoplasmic reticulum (ER) Ca2+-ATPase by thapsigargin analogs induces cell death via ER Ca2+ depletion and the unfold protein response. J. Bio. Chem. 292 (48): 19656-19673.
Wenzel-Seifert K, Krautwurst D, Musgrave I, Seifert R (1996) Thapsigargin activates univalent – and bivalent cation entry in human neutrophils by SKF96365- and Gd3+-sensitive G proteins and protein phosphatases 1/2A and 2B in the signal transduction pathway. Biochem. J. 314: 679-686.
Krause K-H, Demaurex N, Jaconi M and Lew DP (1993) Ion channels and receptors-mediated Ca2+ influx in neutrophils granulocytes. Blood Cells 19: 165-173.
Lytton J, Westlin M, Hanley MR (1991) Thapsigargin inhibits the sarcoplasmic or endoplasmic reticulum Ca2+-ATPase family of calcium pumps. J. Biol. Chem. 266: 17067-17017.
Grune S, Engelking LR, Anwer MS (1993) Role of intracellular calcium and protein kinases in the activation of hepatic Na+/Taurocholate cotransport by cyclic AMP. J. Biol. Chem. 268 (24): 17734-17741.
Tinel H, Wehner F, Sauer H (1994) Intracellular Ca2+ release and Ca2+ influx during regulatory volume decrease in IMCD cells. Am. J. Physiol. 267: 130-8.
Grissmer S, Lewis R, Cahlan MD (1992) Ca2+-activated K+ channels in human leukemic T cells. J. Gen. Physiol. 99: 63-84.
Jäger H, Grissmer S (2004) Characterization of the outer pore region of the apamin-sensitive Ca2+-activated K+ channel rSK2. Toxicon 43 (8): 951-960.
Miller C, Moczydlowski E, Lattore R, Phillips M (1985) Charybdotoxin, a protein-inhibitor of single Ca2+-activated K+ channels from mammalian skeletal muscle. Nature. 313: 316-318.
Yeung CH, Cooper TG (2001) Effects of the ion-channel blocker quinine on human sperm volume, kinematics and mucus penetration, and the involvement of potassium channels. Mol. Hum. Reprod. 7 (9): 819-828.
Verheugen JA, Oortgiesen M, Vijverberg HPM (1994) Veratridine blocks voltage-gated potassium current in human T lymphocytes and in mouse neuroblastoma cells. J. Membr. Biol. 137 (3): 205-214.
Reichstein E, Rothstein A (1981) Effects of quinine on Ca2+-induced K+ efflux from human red blood cells. Journal of membrane Biology 59: 57-63.
Marunaka Y, Niisato N, O’Brodovich H, Post M, Tanswell AK (1999) Roles of Ca2+ and Protein tyrosine kinase in insulin action on cell volume via Na+ and K+ channels and Na+/K+/2Cl- cotranspirter in fetal rat alveolar type II pneumocyte. J. membr. Biol. 168 (1): 91-101.
Ahluwalia J, Tinker A, Clapp LH, Duchen MR, Abramov Ay, Pope S, Nobles M, Segal AW (2004) The large-conductance Ca2+-activated K+ channel is essential for innate immunity. Nature 427: 853-858.
Cox JA, Jeng AY, Sharkey NA, Blumberg PM, Tauber AI (1985) Activation of the human neutrophil nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase by protein kinase C. J. Clin. Invest. 76: 1932-1938.
Ridel A, Lange M, Jazbutyte V, Lotz C, Smul TM, Roewer N, Kehl F (2008) Activation of mitochondrial large-conductance calcium-activated K+ channels via protein kinase A mediates desflurane-induced preconditioning. International Anesthesia research Society 106 (2): 384-391.
Hristov KL, Smith AC, Parajuli SP, Malysz J, Petkov GV (2014) Large-conductance voltage- and Ca2+-activated K+ channel regulation by protein kinase C in guinea pig urinary bladder smooth muscle. Am. J. Physiol. Cell Physiol. 306: C460-C470.
Reiser G, Hamprecht B (1983) Sodium-channels in non-excitable glioma cells, shown by the influence of veratridine, scorpion toxin, and tetrodotoxin on membrane potential and ion transport. Pfluegers. Arch. 397: 260-264.
Villarroel A, Alvarez O, Oberhauser A, Latorre R (1988) Probing a Ca2+-activated K+ channel with quaternary ammonium ions. Pflugers Arch. 413: 118-126.
Bellington SJ, Jost BH, Songer JG (2000) Thiol-activated cytolysins: structure function and role in pathogenesis. FEMS Microbiol. Lett. 182: 197-205.
Repp H, Pamukçi Z, Koschinski A, Domann E, Darji A, Birringer J, Brockmeier D, Chakraborty T, Dreyer F (2002) Listeriolysin of Listeria monocytogenes forms Ca2+-permeable pores leading to intracellular Ca2+ oscillations. Cell. Microbiol. 4 (8): 483-491.
Gurcel L, Abrami L, Girardin S, Tschopp J, Van der Goot FG (2006) Caspase-1 activation of lipid metabolic pathways in response to bacterial pore-forming toxins promotes cell survival. Cell 126: 1135-1145.
Hamon MA, Cossart P (2011) K+ efflux is required for histone H3 dephosphorylation by Listeria monocytogenes Listeriolysin O and other pore-forming toxins. Infection and Immunity 79 (7): 2839-2846.
Vadia S, Seveau S (2014) Fluxes of Ca2+ and K+ are required for the Listeriolysin O-dependent internalization pathway of Listeria monocytogenes. Infection and Immunity 82 (3): 1084-1091.
Aiyar J (1999) Potassium channels in leukocytes and toxins that block them: structure, function and therapeutic implications. Perspect. Drug Discovery Design 15-16: 257-280.
Chandy GK, Wulff H, Beeton C, Pennington M, Gutman GA, Cahalan MD (2004) K+ channels as targets for specific immunomodulation. Trends Pharmacol. Sci. 25: 280-289.
Lazdunski M (1983) Apamin, a neurotoxin specific for one class of Ca2+-dependent K+ channels. Cell Calcium. 4: 421-428.
Cook NS, Haylett DG (1985) Effects of apamin, quinine and neuromuscular blockers on calcium-activated potassium channels in Guinea pig hepatocytes. J. Physiol. 358: 373-394.
Grinstein S, Foskett JK (1990) Ionic mechanisms of cell volume regulation in leukocytes. Ann. Rev. Physiol. 52: 399-414.
Kuriyama H, Kitamura K, Nabata H (1995) Pharmalogical and physiological significance of ion channels and factors that modulate them in vascular tissues. Pharmacol. Rev. 47 (3): 387-573.
Gardos G (1968) The function of calcium in the potassium permeability of human erythrocytes. Bioch. Biophys. Acta. 30: 653-654.
Armando-Hardy M, Ellory JC, Ferreira HG, Fleminger S, Lew VL (1975) Inhibition of the calcium-induced increase in the potassium permeability of human red blood cells by quinine. J. Physiol. 250 (1): 32P-33P.
Brugnara C, De Franceschi L, Alper SL (1993) Ca2+-activated K+ transport in eryhtrocytes-comparison of binding and transport inhibition by scorpion toxins. J. Biol. Chem. 268: 8760-8768.
Hoth M (1996) Depletion of intracellular calcium stores activates an outward potassium current in mast and RBL-1 cells that is corelated with CRAC channel activation. FEBS Letters. 390: 285-288.
Latorre R, Miller C (1983) Conduction and selectivity in potassium channels. Journal of membrane Biology 71: 11-30.
Sarkadi B, Gardos G (1985) Calcium-induced potassium transport in cell membranes. In: Martonosi, A. N. (ed.) The enzymes of biological membranes. 3: 193-234.
Verheugen JA, Vijverberg HPM, Oortgiesen M, Cahalan MD (1995) Voltage-gated and Ca2+-activated K+ channels in intact human T lymphocytes. Nonivasive meaurements of membrane currents, membrane potential, and intracellular calcium. J. Gen. Physiol. 105 (6): 765-794.
Ledoux J, Bonev AD, Nelson MT (2008) Ca2+-activated K+ channels in murine endothelial cels: block by intracellular calcium and magnesium. J. Gen. Physiol. 131 (2): 125-135.
Benton DCH, Roxburgh CJ, Ganellin CR, Shiner MAR, DH Jenkinson (1999) Differences in the action of some blockers of the calcium-activated potassium permeability in mammalian red cells. British Journal of Pharmacology. 126: 169-178.
Pellergrino M, Pellegrini M (1998) Modulation of Ca2+-activated K+ channels of human erythrocytes by endogenous cAMP-dependent protein kinase. Pflugers Arch. 436: 749-756.
Kurokawa Y, Kojima K, Kanayama H, Kagawa S, Minami K, Nakaya Y (1998) Activation of the Ca2+-activated K+ channel via protein kinase A-dependent phosphorylation in human prostatic smooth muscle cells. Int. J. Urol. 5: 482-486.
Peers C, Carpenter E (1998) Inhibition of Ca2+-dependent K+ channels in rat carotid body type I cells by protein kinase C. Journal of Physiology 512 (3): 743-750.
Peppelenbosch MP, Tertoolen LGJ, Laat SW (1991) Epidermal growth factor-activated calcium and potassium channels. Biol. Chem. J. 266: 19938-19944.
Morinaga N, Kato I, Noda M (1993) Changes in the susceptibility of 12-O-Tetradécanoyl-phorbol 13-acetate (TPA)-treated HL-60 cells to staphylococcal leukocidin. Microbiol. Immunol. 37: 537-541.
Bashford CL, Alder GM, Menestrina G, Micklem KJ, Murphy JJ, Pasternak CA (1986) Membrane damage by haemolytic viruses, toxins, complement and other cytotoxic agents: a common mechanism blocked by divalent cations. J. Biol. Chem. 261: 9300-9308.
Chvapil DE (1976) Effect of Zn2+ on cells and bio-membranes. Med. Clin. N. Am. 60: 799-812.
Coote JG (1992) Structural and Functional relationships among the RTX toxin determinants of Gram-negative bacteria. FEMS Microbiol. Rev. 88: 137-162.
Ludwig A, Boebel W (1991) Genetic determinants of cytolytic toxins from Gram-negative bacteria. In: Source Book of Bacterial Protein Toxins. J. E. Alouf and J. H. Freer, editors pp. 147-186. Academic Press, London.
Stavru F, Bouillot F, Sartori A, Ricquier D, Cossart P (2011) Listeria monocytogenes transiently alters mitochondrial dynamics during infection. Proc. Natl. Acad. Sci. U.S.A 108: 3612-3617.
Eiffler I, Behnke J, Ziesemer S, Muller C, Hildebrandt JP (2016) Staphylococcus aureus -toxin-mediated cation entry depolarizes membrane potential and activates p38 MAP kinase in airway epithelial cells. Am. J. Physiol. Lung Cell Mol. Physiol. 311 (3): L676-685.
Genestier AL, Michallet MC, Prevost G, Bellot G, Chalabreysse L, Peyrol S, Thivolet F, Etienne J, Lina G, Valette FM, Vandenesch F, Genestier L (2005) Staphylococcus aureus Panton-Valentine Leukocidin directly targets mitochondria and induces Bax-independent apoptosis of human neutrophils. J. Clin. Invest. 115: 3117-3127.
Colin DA, Mazurier I, Sire S, Finck-Barbançon V (1994) Interaction of the two components of leukocidin from Staphylococcus aureus with human polymorphonuclear leukocyte membranes: sequential binding and subsequent activation. Infect. Immun. 62: 3184-3188.
Colin DA, Monteil H (2003) Control of the oxidative burst of human neutrophils by staphylococcal leukotoxins. Infection and Immunity. 71 (7) 3724-3729.
Schroeder ME, Russo S, Costa C, Hori J, Tiscornia I, Bollati-Fogolin M, Zamboni DS, Ferreira G, Cairoli E, Hill M (2017) Pro-inflammatory Ca2+-activated K+ channels are inhibited by hydroxychloroquine. Scientific Reports 7: 1892.
Bradding P, Wulff H (2009) The K+ channels KCa3.1 and Kv1.3 as novel targets for asthma therapy. Br. J. Pharmacol. 157: 1330-1339.
Gao B, Peigneur S, Tytgat J, Zhu SA (2010) A potent potassium channel blocker from Mesobuthus eupeus scorpion venom. Biochimie 92: 1847-1853.
Wulff H, Castle NA, Pardo LA (2009) Voltage-gated potassium channels as therapeutic targets. Nat. Rev. Drug Discov. 8: 982-1001.
Villalonga N, David M, Bielanska J, Vicente R, Comes N, Valenzuela C, Felipe A (2010) Immunomodulation of voltage-dependent K+ channels in macrophages: Molecular and biophysical consequences. J. Gen. Physiol. 135: 135-147.
Kloft N, Neukirch C, Bobkiewicz W, Veerachato G, Busch T, Von Hoven G, Boller K, Husmann M (2010) Pro-autophagic signal induction by bacterial pore-forming toxins. Med. Microbiol. Immunol. 199: 299-309.
Menzies BE, Kourteva I (2000) Staphylococcus aureus alpha-toxin induces apoptosis in endothelial cells. FEMS Immunol. Med. Microbiol. 29: 39-45.
Imre G, Rajalingam K (2012) Role of caspsase-2 during pore-forming toxin-mediated apoptosis (2012) Cell Cycle 11 (20): 3709-3010.
Löffler B, Huussain M, Grundmeier, Bruck M, Holzinger D, Varga G, Roth J, Kahl BC, Proctor RA, Peters G (2010) Staphylococcus aureus Panton-Valentin Leukocidin is a very potent cytoxic factor in human neutrophils. PloS Pathog. 6 (1): e1000715.
Shan W, Bu S, Zhang C, Ding B, Chang W, Dai Y, Shen J, Ma X (2015) LukS-PV, a component of Panton-Valentine Leukocidin, exerts potent activity against acute myeloid leukemia in vitro and in vivo. Int. J. Biochem. Cell. Biol. 61: 20-28.
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