Staphylococcal alpha-toxin, streptolysin-O, and Escherichia coli hemolysin: prototypes of pore-forming bacterial cytolysins

Bhakdi, Sucharit; Bayley, Hagan; Valeva, Angela; Walev, Iwan; Walker, Barbara; Weller, U.; Kehoe, Michael; Palmer, Michaël

doi:10.1007/s002030050300

Cited by 276 publications

(200 citation statements)

References 37 publications

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“…The two latter toxins are both pore-forming proteins, of which streptolysin O is rather unspecific, whereas CPE possesses specificity in action. [15][16][17] The targeted action of CPE is mediated by binding to a subset of claudins, mainly to claudin-3 and -4, which are frequently overexpressed in epithelial tumors. 22,24,25 This binding leads to disintegration of plasma membrane in association with rapid cytolysis of treated cells.…”

Section: Discussionmentioning

confidence: 99%

“…[5][6][7][8][10][11][12][13][14] Alternatively, the pore-forming bacterial toxins streptolysin O (Streptococcus pyrogenes) and Clostridium perfringens enterotoxin (CPE) came into focus as promising cancer therapeutics. [15][16][17][18] CPE is produced by the anaerobic gram-positive Clostridium perfringens type A strain, known to cause food poisoning. 19 CPE is a 35-kDa protein, which increases cell membrane permeability by formation of large prepore complexes.…”

Section: Introductionmentioning

confidence: 99%

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Novel Clostridium perfringens enterotoxin suicide gene therapy for selective treatment of claudin-3- and -4-overexpressing tumors

et al. 2011

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Bacterial toxins are known to be effective for cancer therapy. Clostridium perfringens enterotoxin (CPE) is produced by the bacterial Clostridium type A strain. The transmembrane proteins claudin-3 and -4, often overexpressed in numerous human epithelial tumors (for example, colon, breast, pancreas, prostate and ovarian), are the targeted receptors for CPE. CPE binding to them triggers formation of membrane pore complexes leading to rapid cell death. In this study, we aimed at selective tumor cell killing by CPE gene transfer. We generated expression vectors bearing the bacterial wild-type CPE cDNA (wtCPE) or translationoptimized CPE (optCPE) cDNA for in vitro and in vivo gene therapy of claudin-3-and -4-overexpressing tumors. The CPE expression analysis at messenger RNA and protein level revealed more efficient expression of optCPE compared with wtCPE. Expression of optCPE showed rapid cytotoxic activity, hightened by CPE release as bystander effect. Cytotoxicity of up to 100% was observed 72 h after gene transfer and is restricted to claudin-3-and -4-expressing tumor lines. MCF-7 and HCT116 cells with high claudin-4 expression showed dramatic sensitivity toward CPE toxicity. The claudin-negative melanoma line SKMel-5, however, was insensitive toward CPE gene transfer. The non-viral intratumoral in vivo gene transfer of optCPE led to reduced tumor growth in MCF-7 and HCT116 tumor-bearing mice compared with the vector-transfected control groups. This novel approach demonstrates that CPE gene transfer can be employed for a targeted suicide gene therapy of claudin-3-and -4-overexpressing tumors, leading to the rapid and efficient tumor cell killing in vitro and in vivo.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Novel Clostridium perfringens enterotoxin suicide gene therapy for selective treatment of claudin-3- and -4-overexpressing tumors

et al. 2011

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“…MEF or MC.Fas À/À cells were plated (2 Â 10 4 cell/well, triplicates, 96-well plates) and cultured overnight in MEM ( þ 5% FCS). Adherent cells were washed with PBS ( Â 2) and incubated with the indicated amounts of the following preparations: pro-gzmB, gzmB, SN from mast cells, SLO 46 or mixtures of SLO and pro-gzmB or gzmB, for 4 h or 24 h. In some experiments, gzmB or mast cell SN were pre-incubated with 100 mM AAD-cmk (Bachem) for 30 min at 371C to inactivate gzmB. Following treatment for 4 h/24 h, survival of MEFs/MC.Fas À/À cells was monitored as described previously.…”

Section: Discussionmentioning

confidence: 99%

Granzyme B is expressed in mouse mast cells in vivo and in vitro and causes delayed cell death independent of perforin

Pardo

Wallich

Ebnet³

et al. 2007

Cell Death Differ

122

130

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Mast cells respond to pathogens and allergens by secreting a vast array of preformed and newly synthesized mediators, including enzymes, vasoactive amines, lipid mediators, cytokines and chemokines, thereby affecting innate and adaptive immune responses and pathogenesis. Here, we present evidence that skin-, but not lung-associated primary mast cells as well as in vitro-differentiated bone marrow-derived mast cells (BMMC) express granzyme (gzm) B, but not gzmA or perforin (perf). GzmB is associated with cytoplasmic granules of BMMC and secreted after Fce-receptor-mediated activation. BMMC from wild type but not gzmB-deficient mice cause cell death in susceptible adherent target cells, indicating that the perf-independent cytotoxicity of BMMC is executed by gzmB. Furthermore, gzmB induces a disorganization of endothelial cell-cell contacts. The data suggest that activated mast cells contribute, via secreted gzmB, to cell death, increased vascular permeability, leukocyte extravasation and subsequent inflammatory processes in affected tissues.

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“…Hemolysins have been isolated and purified from many bacterial pathogens, and they are generally important virulence factors with broad cytolytic activities (Baker and Edwards, 1995;Bhakdi and Tranum-Jensen, 1991;Bhakdi et al, 1990Bhakdi et al, , 1996Cavalieri et al, 1984;Feldman et al, 1990;Grimminger et al, 1991;Johnson et al, 1985;O'Reilly et al, 1986;Ou et al, 1988;Van Der Vijer et al, 1975). The range of cytolytic and other effects associated with different bacterial hemolysins is summarized in Table III, but this is by no means an exhaustive list of either bacterial hemolysins or their effects.…”

Section: Cytolytic Activity Of Bacterial Hemolysinsmentioning

confidence: 99%

Possible Role of Fungal Hemolysins in Sick Building Syndrome

Vesper

2004

Advances in Applied Microbiology

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Staphylococcal alpha-toxin, streptolysin-O, and Escherichia coli hemolysin: prototypes of pore-forming bacterial cytolysins

Cited by 276 publications

References 37 publications

Novel Clostridium perfringens enterotoxin suicide gene therapy for selective treatment of claudin-3- and -4-overexpressing tumors

Novel Clostridium perfringens enterotoxin suicide gene therapy for selective treatment of claudin-3- and -4-overexpressing tumors

Granzyme B is expressed in mouse mast cells in vivo and in vitro and causes delayed cell death independent of perforin

Possible Role of Fungal Hemolysins in Sick Building Syndrome

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