Pomerantsev, Andrei P., Pomerantseva, Olga M., Leppla, Stephen H.
Transformation of Bacillus anthracis with plasmid pUTE29-plcR-papR carrying the native Bacillus cereus plcR-papR gene cluster did not activate expression of B. anthracis hemolysin genes, even though...
The Exotoxin of P. aeruginosa: A Proenzyme Having an Unusual Mode of Activation (2006)
Leppla, Stephen H., Muehl, Laura A., Martin, Ona C.
The exotoxin of Pseudomonas aerguinosa is a proenzyme possessing latent ADPR-transferase activity. Conversion to the active form can be effected by simultaneous treatment with a protein denaturant...
An antibody-based microarray assay for small RNA detection (2006)
Hu, Zonglin, Zhang, Aixia, Storz, Gisela, Gottesman, Susan, Leppla, Stephen H.
Detection of RNAs on microarrays is rapidly becoming a standard approach for molecular biologists. However, current methods frequently discriminate against structured and/or small RNA species. Here...
Production and Purification of Anthrax Toxin (2005)
The three protein components of anthrax toxin can be safely produced and separated from each other using newly developed conditions for growth of Bacillus anthracis and recovery of culture...
Leppla, Stephen H., Ivins, Bruce E.
Anthrax toxin is a key virulence factor of Bacillus anthracis. The three protein components of the toxin have been purified and shown to have similar molecular weights: protective antigen (PA),...
Crystallization of the Protective Antigen Protein of Bacillus anthracis (2003)
Allured, Viloya S., Case, Lisa M., Leppla, Stephen H., McKay, David B.
The protective antigen protein, one of the three separate proteins constituting the exotoxin system of Bacillus anthracis, has been crystallized in a form suitable for high resolution structural...
Little, Stephen F., Leppla, Stephen H., Cora, Elsa
Thirty-six monoclonal antibodies to the protective antigen protein of Bacillus anthracis exotoxin have been characterized for affinity, antibody sub- type, competitive binding to antigenic regions,...
Little, Stephen F., Leppla, Stephen H., Friedlander, Arthur 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...
Effects of Lectins on the Interaction of Diphtheria Toxin with Mammalian Cells. (2002)
Middlebrook,John L., Dorland,Rebecca B., Leppla,Stephen H.
The effects of concanavalin A (Con A) on diphtheria toxin-cell receptor interactions were studied. Con A had no measurable effect on toxin-receptor binding at 4 C but increased the total...
Receptor-mediated Internalization and Degradation of Diphtheria Toxin by Monkey Kidney Cells. (2002)
Dorland,Rebecca B., Middlebrook,John L., Leppla,Stephen H.
The receptor-mediated internalization and degradation of radiolabeled diphtheria toxin by cultured monkey kidney cells was studied. The ability of a number of enzymes and chemicals to remove cell...
Little, Stephen F., Leppla, Stephen H., Cora, Elsa
Thirty-six monoclonal antibodies to the protective antigen of Bacillus anthracis exotoxin have been characterized for affinity, antibody subtype, competitive binding to antigenic regions, and ability...
Goletz, Theresa J., Klimpel, Kurt R., Arora, Naveen, Leppla, Stephen H., Keith, Jerry M., Berzofsky, Jay A.
A challenge for subunit vaccines whose goal is to elicit CD8+ cytotoxic T lymphocytes (CTLs) is to deliver the antigen to the cytosol of the living cell, where it can be processed for presentation by...
Singh, Yogendra, Klimpel, Kurt R., Goel, Seema, Swain, Prabodha K., Leppla, Stephen H.
The protective antigen (PA) protein of anthrax toxin binds to a cellular receptor and is cleaved by cell surface furin to produce a 63-kDa fragment (PA63). The receptor-bound PA63 oligomerizes to a...
Varughese, Mini, Teixeira, Avelino V., Liu, Shihui, Leppla, Stephen H.
Anthrax toxin from Bacillus anthracis is a three-component toxin consisting of lethal factor (LF), edema factor (EF), and protective antigen (PA). LF and EF are the catalytic components of the toxin,...
Proteasome Activity Is Required for Anthrax Lethal Toxin To Kill Macrophages
Tang, Guangqing, Leppla, Stephen H.
Anthrax lethal toxin (LeTx), consisting of protective antigen (PA) and lethal factor (LF), rapidly kills primary mouse macrophages and macrophage-like cell lines such as RAW 264.7. LF is translocated...
Price, Brian M., Liner, Adriane L., Park, Sukjoon, Leppla, Stephen H., Mateczun, Alfred, Galloway, Darrell R.
The ability of genetic vaccination to protect against a lethal challenge of anthrax toxin was evaluated. BALB/c mice were immunized via gene gun inoculation with eucaryotic expression vector plasmids...
Singh, Yogendra, Ivins, Bruce E., Leppla, Stephen H.
Protective antigen (PA) of anthrax toxin is the major component of human anthrax vaccine. Currently available human vaccines in the United States and Europe consist of alum-precipitated supernatant...
Potent antitumor activity of a urokinase-activated engineered anthrax toxin
Liu, Shihui, Aaronson, Hannah, Mitola, David J., Leppla, Stephen H., Bugge, Thomas H.
The acquisition of cell-surface urokinase plasminogen activator activity is a hallmark of malignancy. We generated an engineered anthrax toxin that is activated by cell-surface urokinase in vivo and...
Development of an improved vaccine for anthrax
Leppla, Stephen H., Robbins, John B., Schneerson, Rachel, Shiloach, Joseph
Anthrax lethal factor represses glucocorticoid and progesterone receptor activity
Webster, Jeanette I., Tonelli, Leonardo H., Moayeri, Mahtab, Simons, S. Stoney, Leppla, Stephen H., Sternberg, Esther M.
We report here that a bacterial toxin, anthrax lethal toxin (LeTx), at very low concentrations represses glucocorticoid receptor (GR) transactivation in a transient transfection system and the...
Schneerson, Rachel, Kubler-Kielb, Joanna, Liu, Teh-Yung, Dai, Zhong-Dong, Leppla, Stephen H., Yergey, Alfred, ...
Both the protective antigen (PA) and the poly(γ-d-glutamic acid) capsule (γdPGA) are essential for the virulence of Bacillus anthracis. A critical level of vaccine-induced IgG anti-PA confers...
Bacillus anthracis lethal toxin induces TNF-α–independent hypoxia-mediated toxicity in mice
Moayeri, Mahtab, Haines, Diana, Young, Howard A., Leppla, Stephen H.
Bacillus anthracis lethal toxin (LT) is the major virulence factor of anthrax and reproduces most of the laboratory manifestations of the disease in animals. We studied LT toxicity in BALB/cJ and...
Protection against Anthrax Toxemia by Hexa-d-Arginine In Vitro and In Vivo
Sarac, Miroslav S., Peinado, Juan R., Leppla, Stephen H., Lindberg, Iris
The anthrax toxin protective antigen precursor is activated by proteolytic cleavage by furin or a furin-like protease. We present here data demonstrating that the small stable furin inhibitor...
Moayeri, Mahtab, Martinez, Nathaniel W., Wiggins, Jason, Young, Howard A., Leppla, Stephen H.
Bacillus anthracis lethal toxin (LT) produces symptoms of anthrax in mice and induces rapid lysis of macrophages (Mφ) derived from certain inbred strains. We used nine inbred strains and two...
Pomerantsev, Andrei P., Pomerantseva, Olga M., Leppla, Stephen H.
Transformation of Bacillus anthracis with plasmid pUTE29-plcR-papR carrying the native Bacillus cereus plcR-papR gene cluster did not activate expression of B. anthracis hemolysin genes, even though...
Liu, Shihui, Milne, G. Todd, Kuremsky, Jeffrey G., Fink, Gerald R., Leppla, Stephen H.
Diphthamide, a posttranslational modification of translation elongation factor 2 that is conserved in all eukaryotes and archaebacteria and is the target of diphtheria toxin, is formed in yeast by...
Koya, Vijay, Moayeri, Mahtab, Leppla, Stephen H., Daniell, Henry
The currently available human vaccine for anthrax, derived from the culture supernatant of Bacillus anthracis, contains the protective antigen (PA) and traces of the lethal and edema factors, which...
Peachman, Kristina K., Rao, Mangala, Alving, Carl R., Burge, Robert, Leppla, Stephen H., Rao, Venigalla B., ...
Transcutaneous immunization of mice with recombinant protective antigen (rPA) of Bacillus anthracis resulted in significantly higher lethal toxin-neutralizing antibody titers than did intramuscular...
Genome Engineering in Bacillus anthracis Using Cre Recombinase
Pomerantsev, Andrei P., Sitaraman, Ramakrishnan, Galloway, Craig R., Kivovich, Violetta, Leppla, Stephen H.
Genome engineering is a powerful method for the study of bacterial virulence. With the availability of the complete genomic sequence of Bacillus anthracis, it is now possible to inactivate or delete...
Endocrine Perturbation Increases Susceptibility of Mice to Anthrax Lethal Toxin
Moayeri, Mahtab, Webster, Jeanette I., Wiggins, Jason F., Leppla, Stephen H., Sternberg, Esther M.
Bacillus anthracis lethal toxin (LT) causes vascular collapse and high lethality in BALB/cJ mice, intermediate lethality in C57BL/6J mice, and no lethality in DBA/2J mice. We found that...
Karginov, Vladimir A., Nestorovich, Ekaterina M., Moayeri, Mahtab, Leppla, Stephen H., Bezrukov, Sergey M.
Bacillus anthracis secretes three polypeptides: protective antigen (PA), lethal factor (LF), and edema factor (EF), which interact at the surface of mammalian cells to form toxic complexes. LF and EF...
Anthrax Lethal Toxin Induces Ketotifen-Sensitive Intradermal Vascular Leakage in Certain Inbred Mice
Gozes, Yehoshua, Moayeri, Mahtab, Wiggins, Jason F., Leppla, Stephen H.
Bacillus anthracis lethal toxin (LT) is a bipartite toxin composed of protective antigen (PA) and lethal factor (LF). Injection of LT produces clinical signs characteristic of anthrax infection,...
An antibody-based microarray assay for small RNA detection
Hu, Zonglin, Zhang, Aixia, Storz, Gisela, Gottesman, Susan, Leppla, Stephen H.
Detection of RNAs on microarrays is rapidly becoming a standard approach for molecular biologists. However, current methods frequently discriminate against structured and/or small RNA species. Here...
Dph3, a Small Protein Required for Diphthamide Biosynthesis, Is Essential in Mouse Development
Liu, Shihui, Wiggins, Jason F., Sreenath, Taduru, Kulkarni, Ashok B., Ward, Jerrold M., Leppla, Stephen H.
The translation elongation factor 2 in eukaryotes (eEF-2) contains a unique posttranslationally modified histidine residue, termed diphthamide, which serves as the only target for diphtheria toxin...
Oxidized ATP Protection against Anthrax Lethal Toxin
Moayeri, Mahtab, Wickliffe, Katherine E., Wiggins, Jason F., Leppla, Stephen H.
Bacillus anthracis lethal toxin (LT) induces rapid lysis (
Cisplatin Inhibition of Anthrax Lethal Toxin
Moayeri, Mahtab, Wiggins, Jason F., Lindeman, Robin E., Leppla, Stephen H.
Bacillus anthracis lethal toxin (LT) produces symptoms of anthrax in mice and induces rapid lysis of macrophages derived from certain inbred strains. LT is comprised of a receptor binding component,...
Goletz, Theresa J., Klimpel, Kurt R., Arora, Naveen, Leppla, Stephen H., Keith, Jerry M., Berzofsky, Jay A.
A challenge for subunit vaccines whose goal is to elicit CD8+ cytotoxic T lymphocytes (CTLs) is to deliver the antigen to the cytosol of the living cell, where it can be processed for presentation by...
Singh, Yogendra, Klimpel, Kurt R., Goel, Seema, Swain, Prabodha K., Leppla, Stephen H.
The protective antigen (PA) protein of anthrax toxin binds to a cellular receptor and is cleaved by cell surface furin to produce a 63-kDa fragment (PA63). The receptor-bound PA63 oligomerizes to a...
Varughese, Mini, Teixeira, Avelino V., Liu, Shihui, Leppla, Stephen H.
Anthrax toxin from Bacillus anthracis is a three-component toxin consisting of lethal factor (LF), edema factor (EF), and protective antigen (PA). LF and EF are the catalytic components of the toxin,...
Proteasome Activity Is Required for Anthrax Lethal Toxin To Kill Macrophages
Tang, Guangqing, Leppla, Stephen H.
Anthrax lethal toxin (LeTx), consisting of protective antigen (PA) and lethal factor (LF), rapidly kills primary mouse macrophages and macrophage-like cell lines such as RAW 264.7. LF is translocated...
Price, Brian M., Liner, Adriane L., Park, Sukjoon, Leppla, Stephen H., Mateczun, Alfred, Galloway, Darrell R.
The ability of genetic vaccination to protect against a lethal challenge of anthrax toxin was evaluated. BALB/c mice were immunized via gene gun inoculation with eucaryotic expression vector plasmids...
Singh, Yogendra, Ivins, Bruce E., Leppla, Stephen H.
Protective antigen (PA) of anthrax toxin is the major component of human anthrax vaccine. Currently available human vaccines in the United States and Europe consist of alum-precipitated supernatant...
Potent antitumor activity of a urokinase-activated engineered anthrax toxin
Liu, Shihui, Aaronson, Hannah, Mitola, David J., Leppla, Stephen H., Bugge, Thomas H.
The acquisition of cell-surface urokinase plasminogen activator activity is a hallmark of malignancy. We generated an engineered anthrax toxin that is activated by cell-surface urokinase in vivo and...
Development of an improved vaccine for anthrax
Leppla, Stephen H., Robbins, John B., Schneerson, Rachel, Shiloach, Joseph
Anthrax lethal factor represses glucocorticoid and progesterone receptor activity
Webster, Jeanette I., Tonelli, Leonardo H., Moayeri, Mahtab, Simons, S. Stoney, Leppla, Stephen H., Sternberg, Esther M.
We report here that a bacterial toxin, anthrax lethal toxin (LeTx), at very low concentrations represses glucocorticoid receptor (GR) transactivation in a transient transfection system and the...
Schneerson, Rachel, Kubler-Kielb, Joanna, Liu, Teh-Yung, Dai, Zhong-Dong, Leppla, Stephen H., Yergey, Alfred, ...
Both the protective antigen (PA) and the poly(γ-d-glutamic acid) capsule (γdPGA) are essential for the virulence of Bacillus anthracis. A critical level of vaccine-induced IgG anti-PA confers...
Bacillus anthracis lethal toxin induces TNF-α–independent hypoxia-mediated toxicity in mice
Moayeri, Mahtab, Haines, Diana, Young, Howard A., Leppla, Stephen H.
Bacillus anthracis lethal toxin (LT) is the major virulence factor of anthrax and reproduces most of the laboratory manifestations of the disease in animals. We studied LT toxicity in BALB/cJ and...
Protection against Anthrax Toxemia by Hexa-d-Arginine In Vitro and In Vivo
Sarac, Miroslav S., Peinado, Juan R., Leppla, Stephen H., Lindberg, Iris
The anthrax toxin protective antigen precursor is activated by proteolytic cleavage by furin or a furin-like protease. We present here data demonstrating that the small stable furin inhibitor...
Moayeri, Mahtab, Martinez, Nathaniel W., Wiggins, Jason, Young, Howard A., Leppla, Stephen H.
Bacillus anthracis lethal toxin (LT) produces symptoms of anthrax in mice and induces rapid lysis of macrophages (Mφ) derived from certain inbred strains. We used nine inbred strains and two...
Pomerantsev, Andrei P., Pomerantseva, Olga M., Leppla, Stephen H.
Transformation of Bacillus anthracis with plasmid pUTE29-plcR-papR carrying the native Bacillus cereus plcR-papR gene cluster did not activate expression of B. anthracis hemolysin genes, even though...
Liu, Shihui, Milne, G. Todd, Kuremsky, Jeffrey G., Fink, Gerald R., Leppla, Stephen H.
Diphthamide, a posttranslational modification of translation elongation factor 2 that is conserved in all eukaryotes and archaebacteria and is the target of diphtheria toxin, is formed in yeast by...
Endocrine Perturbation Increases Susceptibility of Mice to Anthrax Lethal Toxin
Moayeri, Mahtab, Webster, Jeanette I., Wiggins, Jason F., Leppla, Stephen H., Sternberg, Esther M.
Bacillus anthracis lethal toxin (LT) causes vascular collapse and high lethality in BALB/cJ mice, intermediate lethality in C57BL/6J mice, and no lethality in DBA/2J mice. We found that...
Karginov, Vladimir A., Nestorovich, Ekaterina M., Moayeri, Mahtab, Leppla, Stephen H., Bezrukov, Sergey M.
Bacillus anthracis secretes three polypeptides: protective antigen (PA), lethal factor (LF), and edema factor (EF), which interact at the surface of mammalian cells to form toxic complexes. LF and EF...
Koya, Vijay, Moayeri, Mahtab, Leppla, Stephen H., Daniell, Henry
The currently available human vaccine for anthrax, derived from the culture supernatant of Bacillus anthracis, contains the protective antigen (PA) and traces of the lethal and edema factors, which...
Peachman, Kristina K., Rao, Mangala, Alving, Carl R., Burge, Robert, Leppla, Stephen H., Rao, Venigalla B., ...
Transcutaneous immunization of mice with recombinant protective antigen (rPA) of Bacillus anthracis resulted in significantly higher lethal toxin-neutralizing antibody titers than did intramuscular...
Genome Engineering in Bacillus anthracis Using Cre Recombinase
Pomerantsev, Andrei P., Sitaraman, Ramakrishnan, Galloway, Craig R., Kivovich, Violetta, Leppla, Stephen H.
Genome engineering is a powerful method for the study of bacterial virulence. With the availability of the complete genomic sequence of Bacillus anthracis, it is now possible to inactivate or delete...
Anthrax Lethal Toxin Induces Ketotifen-Sensitive Intradermal Vascular Leakage in Certain Inbred Mice
Gozes, Yehoshua, Moayeri, Mahtab, Wiggins, Jason F., Leppla, Stephen H.
Bacillus anthracis lethal toxin (LT) is a bipartite toxin composed of protective antigen (PA) and lethal factor (LF). Injection of LT produces clinical signs characteristic of anthrax infection,...
An antibody-based microarray assay for small RNA detection
Hu, Zonglin, Zhang, Aixia, Storz, Gisela, Gottesman, Susan, Leppla, Stephen H.
Detection of RNAs on microarrays is rapidly becoming a standard approach for molecular biologists. However, current methods frequently discriminate against structured and/or small RNA species. Here...
Dph3, a Small Protein Required for Diphthamide Biosynthesis, Is Essential in Mouse Development
Liu, Shihui, Wiggins, Jason F., Sreenath, Taduru, Kulkarni, Ashok B., Ward, Jerrold M., Leppla, Stephen H.
The translation elongation factor 2 in eukaryotes (eEF-2) contains a unique posttranslationally modified histidine residue, termed diphthamide, which serves as the only target for diphtheria toxin...
Oxidized ATP Protection against Anthrax Lethal Toxin
Moayeri, Mahtab, Wickliffe, Katherine E., Wiggins, Jason F., Leppla, Stephen H.
Bacillus anthracis lethal toxin (LT) induces rapid lysis (
Cisplatin Inhibition of Anthrax Lethal Toxin
Moayeri, Mahtab, Wiggins, Jason F., Lindeman, Robin E., Leppla, Stephen H.
Bacillus anthracis lethal toxin (LT) produces symptoms of anthrax in mice and induces rapid lysis of macrophages derived from certain inbred strains. LT is comprised of a receptor binding component,...
Bacillus anthracis Edema Toxin Causes Extensive Tissue Lesions and Rapid Lethality in Mice
Firoved, Aaron M., Miller, Georgina F., Moayeri, Mahtab, Kakkar, Rahul, Shen, Yuequan, Wiggins, Jason F., ...
Bacillus anthracis edema toxin (ET), an adenylyl cyclase, is an important virulence factor that contributes to anthrax disease. The role of ET in anthrax pathogenesis is, however, poorly understood....
Anthrax Toxins Induce Shock in Rats by Depressed Cardiac Ventricular Function
Watson, Linley E., Kuo, Shu-ru, Katki, Khurshed, Dang, Tongyun, Park, Seong Kyu, Dostal, David E., ...
Anthrax infections are frequently associated with severe and often irreversible hypotensive shock. The isolated toxic proteins of Bacillus anthracis produce a non-cytokine-mediated hypotension in...
Anthrax Edema Toxin Sensitizes DBA/2J Mice to Lethal Toxin▿
Firoved, Aaron M., Moayeri, Mahtab, Wiggins, Jason F., Shen, Yuequan, Tang, Wei-Jen, Leppla, Stephen H.
Anthrax toxin is made up of three separate protein components: the receptor-binding protective antigen (PA), the adenylyl cyclase edema factor (EF), and the metalloproteinase lethal factor (LF). EF...
Receptor palmitoylation and ubiquitination regulate anthrax toxin endocytosis
Abrami, Laurence, Leppla, Stephen H., Van Der Goot, F. Gisou
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),...
Anthrax Protective Antigen Cleavage and Clearance from the Blood of Mice and Rats▿
Moayeri, Mahtab, Wiggins, Jason F., Leppla, Stephen H.
Bacillus anthracis protective antigen (PA) is an 83-kDa (PA83) protein that is cleaved to the 63-kDa protein (PA63) as an essential step in binding and internalizing lethal factor (LF). To assess in...
Abrami, Laurence, Lindsay, Margaret, Parton, Robert G., Leppla, Stephen H., Van Der Goot, F. Gisou
The protective antigen (PA) of anthrax toxin binds to a cell surface receptor, undergoes heptamerization, and binds the enzymatic subunits, the lethal factor (LF) and the edema factor (EF). The...
Abrami, Laurence, Liu, Shihui, Cosson, Pierre, Leppla, Stephen H., Van Der Goot, F. Gisou
The protective antigen (PA) of the anthrax toxin binds to a cell surface receptor and thereby allows lethal factor (LF) to be taken up and exert its toxic effect in the cytoplasm. Here, we report...
Role of N-Terminal Amino Acids in the Potency of Anthrax Lethal Factor
Gupta, Pradeep K., Moayeri, Mahtab, Crown, Devorah, Fattah, Rasem J., Leppla, Stephen H.
Anthrax lethal factor (LF) is a Zn+2-dependent metalloprotease that cleaves several MAPK kinases and is responsible for the lethality of anthrax lethal toxin (LT). We observed that a recombinant LF...
In Vivo Efficacy of β-Cyclodextrin Derivatives against Anthrax Lethal Toxin▿
Moayeri, Mahtab, Robinson, Tanisha M., Leppla, Stephen H., Karginov, Vladimir A.
We evaluated the in vivo efficacy of three β-cyclodextrin derivatives that block the anthrax protective antigen pore. These compounds were at least 15-fold more potent than previously described...
Kubler-Kielb, Joanna, Vinogradov, Evgeny, Hu, Haijing, Leppla, Stephen H., Robbins, John B., Schneerson, Rachel
Bacillus anthracis is a spore-forming bacterium that causes anthrax in humans and in other mammals. The glycoprotein BclA (Bacillus collagen-like protein of anthracis) is a major constituent of the...
Moayeri, Mahtab, Crown, Devorah, Dorward, David W., Gardner, Don, Ward, Jerrold M., Li, Yan, ...
Anthrax lethal toxin (LT) induces vascular insufficiency in experimental animals through unknown mechanisms. In this study, we show that neuronal nitric oxide synthase (nNOS) deficiency in mice...
Detection of Anthrax Toxin by an Ultrasensitive Immunoassay Using Europium Nanoparticles▿
Tang, Shixing, Moayeri, Mahtab, Chen, Zhaochun, Harma, Harri, Zhao, Jiangqin, Hu, Haijing, ...
We developed a europium nanoparticle-based immunoassay (ENIA) for the sensitive detection of anthrax protective antigen (PA). The ENIA exhibited a linear dose-dependent pattern within the detection...
Codon-Optimized Fluorescent Proteins Designed for Expression in Low-GC Gram-Positive Bacteria▿
Sastalla, Inka, Chim, Kannie, Cheung, Gordon Y. C., Pomerantsev, Andrei P., Leppla, Stephen H.
Fluorescent proteins have wide applications in biology. However, not all of these proteins are properly expressed in bacteria, especially if the codon usage and genomic GC content of the host...