S. H. Leppla

Publication List Details

Period

1998 - 2006

Number

57

Co-Authors

Receptor palmitoylation and ubiquitination regulate anthrax toxin endocytosis (2006)

Abrami, L., Leppla, S. H., Van Der Goot, F. G.

The anthrax toxin is composed of three independent polypeptide chains. Successful intoxication only occurs when heptamerization of the receptor-binding polypeptide, the protective antigen (PA),...

Antibodies to Anthrax Toxin in Humans and Guinea Pigs and Their Relevance to Protective Immunity (1998)

Turnbull, P. C., Leppla, S. H., Broster, M. G., Quinn, C. P., Melling, J.

A forerunning study on the relationship between antibodies to the protective antigen (PA) and lethal factor (LF) components of anthrax toxin and protective immunity has been expanded and extended to...

The pore-forming toxin proaerolysin is activated by furin (1998)

Abrami, L., Fivaz, M., Decroly, E., Seidah, N. G., Jean, F., Thomas, G., ...

Aerolysin is secreted as an inactive dimeric precursor by the bacterium Aeromonas hydrophila. Proteolytic cleavage within a mobile loop near the C terminus of the protoxin is required for...

Suppression of ras-mediated transformation and inhibition of tumor growth and angiogenesis by anthrax lethal factor, a proteolytic inhibitor of multiple MEK pathways

Duesbery, N. S., Resau, J., Webb, C. P., Koochekpour, S., Leppla, S. H., ...

Lethal factor is a protease, one component of Bacillus anthracis exotoxin, which cleaves many of the mitogen-activated protein kinase kinases (MEKs). Given the importance of MEK signaling in...

Anthrax toxin protective antigen is activated by a cell surface protease with the sequence specificity and catalytic properties of furin.

Klimpel, K R, Molloy, S S, Thomas, G, Leppla, S H

Proteolytic cleavage of the protective antigen (PA) protein of anthrax toxin at residues 164-167 is necessary for toxic activity. Cleavage by a cellular protease at this sequence, Arg-Lys-Lys-Arg,...

Proteolytic activation of bacterial toxins by eukaryotic cells is performed by furin and by additional cellular proteases.

Gordon, V M, Klimpel, K R, Arora, N, Henderson, M A, Leppla, S H

Before intoxication can occur, anthrax toxin protective antigen (PA), Pseudomonas exotoxin A (PE), and diphtheria toxin (DT) must be activated by proteolytic cleavage at specific amino acid...

Furin regulates both the activation of Pseudomonas exotoxin A and the Quantity of the toxin receptor expressed on target cells.

Gu, M, Gordon, V M, Fitzgerald, D J, Leppla, S H

Pseudomonas exotoxin A (PE) binds and enters mammalian cells via the alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein (LRP). The toxin then requires proteolytic...

A role for PACE4 in the proteolytic activation of anthrax toxin protective antigen.

Gordon, V M, Rehemtulla, A, Leppla, S H

Several bacterial protein toxins require activation by eukaryotic proteases. Previous studies have shown that anthrax toxin protective antigen (PA), Pseudomonas exotoxin A (PE), and diphtheria toxin...

Clostridium septicum alpha-toxin is proteolytically activated by furin.

Gordon, V M, Benz, R, Fujii, K, Leppla, S H, Tweten, R K

Clostridium septicum alpha-toxin is secreted as an inactive 46,450-Da protoxin. The protoxin is activated by proteolytic cleavage near the C terminus, which eventually causes the release of a...

Cloning and characterization of a gene whose product is a trans-activator of anthrax toxin synthesis.

Uchida, I, Hornung, J M, Thorne, C B, Klimpel, K R, Leppla, S H

The 184-kb Bacillus anthracis plasmid pXO1, which is required for virulence, contains three genes encoding the protein components of anthrax toxin, cya (edema factor gene), lef (lethal factor gene),...

Phosphatidylcholine-Specific Phospholipase C and Sphingomyelinase Activities in Bacteria of the Bacillus cereus Group

Pomerantsev, A. P., Kalnin, K. V., Osorio, M., Leppla, S. H.

Bacillus anthracis is nonhemolytic, even though it is closely related to the highly hemolytic Bacillus cereus. Hemolysis by B. cereus results largely from the action of phosphatidylcholine-specific...

Production and characterization of monoclonal antibodies against the lethal factor component of Bacillus anthracis lethal toxin.

Little, S F, Leppla, S H, Friedlander, A M

The lethal toxin of Bacillus anthracis consists of two components, protective antigen and lethal factor. Protective antigen is cleaved after binding to cell receptors, yielding a receptor-bound...

Production and characterization of monoclonal antibodies to the protective antigen component of Bacillus anthracis toxin.

Little, S F, Leppla, S H, Cora, E

Thirty-six monoclonal antibodies to the protective antigen protein of Bacillus anthracis exotoxin have been characterized for affinity, antibody subtype, competitive binding to antigenic regions, and...

Inhibitors of receptor-mediated endocytosis block the entry of Bacillus anthracis adenylate cyclase toxin but not that of Bordetella pertussis adenylate cyclase toxin.

Gordon, V M, Leppla, S H, Hewlett, E L

Bordetella pertussis and Bacillus anthracis produce extracytoplasmic adenylate cyclase toxins (AC toxins) with shared features including activation by calmodulin and the ability to enter target cells...

Immunization studies with attenuated strains of Bacillus anthracis.

Ivins, B E, Ezzell, J W, Jemski, J, Hedlund, K W, Ristroph, J D, Leppla, S H

Live, attenuated strains of Bacillus anthracis lacking either the capsule plasmid pXO2, the toxin plasmid pXO1, or both were tested for their efficacy as vaccines against intravenous challenge with...

Immunoelectrophoretic analysis, toxicity, and kinetics of in vitro production of the protective antigen and lethal factor components of Bacillus anthracis toxin.

Ezzell, J W, Ivins, B E, Leppla, S H

The kinetics of Bacillus anthracis toxin production in culture and its lethal activity in rats, mice, and guinea pigs were investigated. Lethal toxin activity was produced in vitro throughout...

Characterization of macrophage sensitivity and resistance to anthrax lethal toxin.

Friedlander, A M, Bhatnagar, R, Leppla, S H, Johnson, L, Singh, Y

Anthrax lethal toxin, which consists of two proteins, protective antigen and lethal factor, is cytolytic for macrophages. Macrophages from different mouse strains were found to vary in their...

Fusions of anthrax toxin lethal factor with shiga toxin and diphtheria toxin enzymatic domains are toxic to mammalian cells.

Arora, N, Leppla, S H

To investigate the ability of anthrax toxin lethal factor (LF) to translocate foreign proteins into the cytosol of eukaryotic cells and to characterize the structural requirements of this process,...

Transcriptional regulation of the protective antigen gene of Bacillus anthracis.

Bartkus, J M, Leppla, S H

Bicarbonate is required for production of the major virulence factors, the toxins and capsule, of Bacillus anthracis. In this study we examined the basis for stimulation of production of protective...

Calcium is required for the expression of anthrax lethal toxin activity in the macrophagelike cell line J774A.1.

Bhatnagar, R, Singh, Y, Leppla, S H, Friedlander, A M

Anthrax lethal toxin, which consists of two separate proteins, protective antigen (Mr, 82,700) and lethal factor (Mr, approximately 83,000), is cytotoxic to the macrophagelike cell line J774A.1....

Anthrax toxin edema factor: a bacterial adenylate cyclase that increases cyclic AMP concentrations of eukaryotic cells.

Leppla, S H

Anthrax toxin is composed of three proteins: protective antigen (PA), lethal factor (LF), and edema factor (EF). These proteins individually cause no known physiological effects in animals but in...

Protection against experimental Pseudomonas aeruginosa infection in mice by active immunization with exotoxin A toxoids.

Pavlovskis, O R, Edman, D C, Leppla, S H, Wretlind, B, Lewis, L R, Martin, K E

The immunoprophylactic effect of chemically inactivated Pseudomonas aeruginosa exotoxin A in experimental pseudomonas infections was studied. Exotoxin A toxoids were prepared by Formalin (f-TXD) or...

Comparison of the 3′ Termini of Discrete Segments of the Double-Stranded Ribonucleic Acid Genomes of Cytoplasmic Polyhedrosis Virus, Wound Tumor Virus, and Reovirus

Lewandowski, Leon J., Leppla, S. H.

The 3′ terminal nucleosides of the isolated components of double-stranded ribonucleic acids of reovirus, wound tumor virus, and cytoplasmic polyhedrosis virus were determined by labeling with...

Characterization of the Subunit Structure of the Ribonucleic Acid Genome of Influenza Virus

Lewandowski, L. J., Content, J., Leppla, S. H.

Ribonucleic acid extracted from influenza virus was labeled at the 3′ termini with 3H and analyzed by polyacrylamide gel electrophoresis. Influenza virus was found to contain a minimum of seven and...

Evaluation of Pseudomonas aeruginosa toxin A in experimental rat burn wound sepsis.

Walker, H L, McLeod, C G, Leppla, S H, Mason, A D

The search for methods to achieve control of Pseudomonas aeruginosa infection continues with the introduction of aluminum-absorbed toxoid developed from P. aeruginosa exotoxin. This toxoid induces...

Large-scale purification and characterization of the exotoxin of Pseudomonas aeruginosa.

Leppla, S H

The exotoxin (PE) of Pseudomonas aeruginosa was purified from 50-liter cultures by a simple three-step procedure, yielding 135 mg of essentially homogeneous protein. In Ouchterlony gel diffusion, PE...

Suppression of ras-mediated transformation and inhibition of tumor growth and angiogenesis by anthrax lethal factor, a proteolytic inhibitor of multiple MEK pathways

Duesbery, N. S., Resau, J., Webb, C. P., Koochekpour, S., Leppla, S. H., ...

Lethal factor is a protease, one component of Bacillus anthracis exotoxin, which cleaves many of the mitogen-activated protein kinase kinases (MEKs). Given the importance of MEK signaling in...

Anthrax toxin protective antigen is activated by a cell surface protease with the sequence specificity and catalytic properties of furin.

Klimpel, K R, Molloy, S S, Thomas, G, Leppla, S H

Proteolytic cleavage of the protective antigen (PA) protein of anthrax toxin at residues 164-167 is necessary for toxic activity. Cleavage by a cellular protease at this sequence, Arg-Lys-Lys-Arg,...

Proteolytic activation of bacterial toxins by eukaryotic cells is performed by furin and by additional cellular proteases.

Gordon, V M, Klimpel, K R, Arora, N, Henderson, M A, Leppla, S H

Before intoxication can occur, anthrax toxin protective antigen (PA), Pseudomonas exotoxin A (PE), and diphtheria toxin (DT) must be activated by proteolytic cleavage at specific amino acid...

Furin regulates both the activation of Pseudomonas exotoxin A and the Quantity of the toxin receptor expressed on target cells.

Gu, M, Gordon, V M, Fitzgerald, D J, Leppla, S H

Pseudomonas exotoxin A (PE) binds and enters mammalian cells via the alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein (LRP). The toxin then requires proteolytic...

A role for PACE4 in the proteolytic activation of anthrax toxin protective antigen.

Gordon, V M, Rehemtulla, A, Leppla, S H

Several bacterial protein toxins require activation by eukaryotic proteases. Previous studies have shown that anthrax toxin protective antigen (PA), Pseudomonas exotoxin A (PE), and diphtheria toxin...

Clostridium septicum alpha-toxin is proteolytically activated by furin.

Gordon, V M, Benz, R, Fujii, K, Leppla, S H, Tweten, R K

Clostridium septicum alpha-toxin is secreted as an inactive 46,450-Da protoxin. The protoxin is activated by proteolytic cleavage near the C terminus, which eventually causes the release of a...

Cloning and characterization of a gene whose product is a trans-activator of anthrax toxin synthesis.

Uchida, I, Hornung, J M, Thorne, C B, Klimpel, K R, Leppla, S H

The 184-kb Bacillus anthracis plasmid pXO1, which is required for virulence, contains three genes encoding the protein components of anthrax toxin, cya (edema factor gene), lef (lethal factor gene),...

Phosphatidylcholine-Specific Phospholipase C and Sphingomyelinase Activities in Bacteria of the Bacillus cereus Group

Pomerantsev, A. P., Kalnin, K. V., Osorio, M., Leppla, S. H.

Bacillus anthracis is nonhemolytic, even though it is closely related to the highly hemolytic Bacillus cereus. Hemolysis by B. cereus results largely from the action of phosphatidylcholine-specific...

Production and characterization of monoclonal antibodies against the lethal factor component of Bacillus anthracis lethal toxin.

Little, S F, Leppla, S H, Friedlander, A M

The lethal toxin of Bacillus anthracis consists of two components, protective antigen and lethal factor. Protective antigen is cleaved after binding to cell receptors, yielding a receptor-bound...

Production and characterization of monoclonal antibodies to the protective antigen component of Bacillus anthracis toxin.

Little, S F, Leppla, S H, Cora, E

Thirty-six monoclonal antibodies to the protective antigen protein of Bacillus anthracis exotoxin have been characterized for affinity, antibody subtype, competitive binding to antigenic regions, and...

Inhibitors of receptor-mediated endocytosis block the entry of Bacillus anthracis adenylate cyclase toxin but not that of Bordetella pertussis adenylate cyclase toxin.

Gordon, V M, Leppla, S H, Hewlett, E L

Bordetella pertussis and Bacillus anthracis produce extracytoplasmic adenylate cyclase toxins (AC toxins) with shared features including activation by calmodulin and the ability to enter target cells...

Immunization studies with attenuated strains of Bacillus anthracis.

Ivins, B E, Ezzell, J W, Jemski, J, Hedlund, K W, Ristroph, J D, Leppla, S H

Live, attenuated strains of Bacillus anthracis lacking either the capsule plasmid pXO2, the toxin plasmid pXO1, or both were tested for their efficacy as vaccines against intravenous challenge with...

Immunoelectrophoretic analysis, toxicity, and kinetics of in vitro production of the protective antigen and lethal factor components of Bacillus anthracis toxin.

Ezzell, J W, Ivins, B E, Leppla, S H

The kinetics of Bacillus anthracis toxin production in culture and its lethal activity in rats, mice, and guinea pigs were investigated. Lethal toxin activity was produced in vitro throughout...

Characterization of macrophage sensitivity and resistance to anthrax lethal toxin.

Friedlander, A M, Bhatnagar, R, Leppla, S H, Johnson, L, Singh, Y

Anthrax lethal toxin, which consists of two proteins, protective antigen and lethal factor, is cytolytic for macrophages. Macrophages from different mouse strains were found to vary in their...

Fusions of anthrax toxin lethal factor with shiga toxin and diphtheria toxin enzymatic domains are toxic to mammalian cells.

Arora, N, Leppla, S H

To investigate the ability of anthrax toxin lethal factor (LF) to translocate foreign proteins into the cytosol of eukaryotic cells and to characterize the structural requirements of this process,...

Transcriptional regulation of the protective antigen gene of Bacillus anthracis.

Bartkus, J M, Leppla, S H

Bicarbonate is required for production of the major virulence factors, the toxins and capsule, of Bacillus anthracis. In this study we examined the basis for stimulation of production of protective...

Calcium is required for the expression of anthrax lethal toxin activity in the macrophagelike cell line J774A.1.

Bhatnagar, R, Singh, Y, Leppla, S H, Friedlander, A M

Anthrax lethal toxin, which consists of two separate proteins, protective antigen (Mr, 82,700) and lethal factor (Mr, approximately 83,000), is cytotoxic to the macrophagelike cell line J774A.1....

Anthrax toxin edema factor: a bacterial adenylate cyclase that increases cyclic AMP concentrations of eukaryotic cells.

Leppla, S H

Anthrax toxin is composed of three proteins: protective antigen (PA), lethal factor (LF), and edema factor (EF). These proteins individually cause no known physiological effects in animals but in...

Protection against experimental Pseudomonas aeruginosa infection in mice by active immunization with exotoxin A toxoids.

Pavlovskis, O R, Edman, D C, Leppla, S H, Wretlind, B, Lewis, L R, Martin, K E

The immunoprophylactic effect of chemically inactivated Pseudomonas aeruginosa exotoxin A in experimental pseudomonas infections was studied. Exotoxin A toxoids were prepared by Formalin (f-TXD) or...

Comparison of the 3′ Termini of Discrete Segments of the Double-Stranded Ribonucleic Acid Genomes of Cytoplasmic Polyhedrosis Virus, Wound Tumor Virus, and Reovirus

Lewandowski, Leon J., Leppla, S. H.

The 3′ terminal nucleosides of the isolated components of double-stranded ribonucleic acids of reovirus, wound tumor virus, and cytoplasmic polyhedrosis virus were determined by labeling with...

Characterization of the Subunit Structure of the Ribonucleic Acid Genome of Influenza Virus

Lewandowski, L. J., Content, J., Leppla, S. H.

Ribonucleic acid extracted from influenza virus was labeled at the 3′ termini with 3H and analyzed by polyacrylamide gel electrophoresis. Influenza virus was found to contain a minimum of seven and...

Evaluation of Pseudomonas aeruginosa toxin A in experimental rat burn wound sepsis.

Walker, H L, McLeod, C G, Leppla, S H, Mason, A D

The search for methods to achieve control of Pseudomonas aeruginosa infection continues with the introduction of aluminum-absorbed toxoid developed from P. aeruginosa exotoxin. This toxoid induces...

Large-scale purification and characterization of the exotoxin of Pseudomonas aeruginosa.

Leppla, S H

The exotoxin (PE) of Pseudomonas aeruginosa was purified from 50-liter cultures by a simple three-step procedure, yielding 135 mg of essentially homogeneous protein. In Ouchterlony gel diffusion, PE...

Internalization of a Bacillus anthracis protective antigen-c-Myc fusion protein mediated by cell surface anti-c-Myc antibodies.

Varughese, M., Chi, A., Teixeira, A. V., Nicholls, P. J., Keith, J. M., Leppla, S. H.

BACKGROUND: Anthrax toxin, secreted by Bacillus anthracis, consists of protective antigen (PA) and either lethal factor (LF) or edema factor (EF). PA, the receptor-binding component of the toxin,...