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9. The Molecular Architecture and Mode of Action of Clostridium perfringens ε-Toxin.

Author

Titball, Richard W.

Subjects
*CLOSTRIDIUM perfringens, *MOLECULAR structure, *MYELIN proteins, *NECROTIC enteritis, *RESEARCH personnel, *MULTIPLE sclerosis, *AMINO acids
Abstract

Clostridium perfringens ε-toxin has long been associated with a severe enterotoxaemia of livestock animals, and more recently, was proposed to play a role in the etiology of multiple sclerosis in humans. The remarkable potency of the toxin has intrigued researchers for many decades, who suggested that this indicated an enzymatic mode of action. Recently, there have been major breakthroughs by finding that it is a pore-forming toxin which shows exquisite specificity for cells bearing the myelin and lymphocyte protein (MAL) receptor. This review details the molecular structures of the toxin, the evidence which identifies MAL as the receptor and the possible roles of other cell membrane components in toxin binding. The information on structure and mode of action has allowed the functions of individual amino acids to be investigated and has led to the creation of mutants with reduced toxicity that could serve as vaccines. In spite of this progress, there are still a number of key questions around the mode of action of the toxin which need to be further investigated. [ABSTRACT FROM AUTHOR]

Published
2024
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11. Genomic Plasticity of the Causative Agent of Melioidosis, Burkholderia pseudomallei

Author

Titball, Richard W., Peacock, Sharon J., Cerdeño-Tárraga, Ana M., Atkins, Timothy, Crossman, Lisa C., Pitt, Tyrone, Churcher, Carol, Mungall, Karen, Bentley, Stephen D., Sebaihia, Mohammed, Thomson, Nicholas R., Bason, Nathalie, Beacham, Ifor R., Brooks, Karen, Brown, Katherine A., Brown, Nat F., Challis, Greg L., Cherevach, Inna, Chillingworth, Tracy, Cronin, Ann, Crossett, Ben, Davis, Paul, DeShazer, David, Feltwell, Theresa, Fraser, Audrey, Hance, Zahra, Hauser, Heidi, Holroyd, Simon, Jagels, Kay, Keith, Karen E., Maddison, Mark, Moule, Sharon, Price, Claire, Quail, Michael A., Rabbinowitsch, Ester, Rutherford, Kim, Sanders, Mandy, Simmonds, Mark, Songsivilai, Sirirurg, Stevens, Kim, Tumapa, Sarinna, Vesaratchavest, Monkgol, Whitehead, Sally, Yeats, Corin, Barrell, Bart G., Parkhill, Julian, and Greenberg, E. Peter

Published
2004

12. Phenotypic and Functional Characterization of Human Memory T Cell Responses to Burkholderia pseudomallei

Author

Tippayawat, Patcharaporn, Saenwongsa, Wipawee, Mahawantung, Jirawan, Suwannasaen, Duangchan, Chetchotisakd, Ploenchan, Limmathurotsakul, Direk, Peacock, Sharon J, Felgner, Philip L, Atkins, Helen S, Titball, Richard W, Bancroft, Gregory J, and Lertmemongkolchai, Ganjana

Subjects
gamma-interferon, ifn-gamma, provides protection, severe melioidosis, adaptive immunity, secretion system, murine model, risk-factors, infection, identification
Abstract

Background: Infection with the Gram-negative bacterium Burkholderia pseudomallei is an important cause of community-acquired lethal sepsis in endemic regions in southeast Asia and northern Australia and is increasingly reported in other tropical areas. In animal models, production of interferon-gamma (IFN-gamma) is critical for resistance, but in humans the characteristics of IFN-gamma production and the bacterial antigens that are recognized by the cell-mediated immune response have not been defined. Methods: Peripheral blood from 133 healthy individuals who lived in the endemic area and had no history of melioidosis, 60 patients who had recovered from melioidosis, and 31 other patient control subjects were stimulated by whole bacteria or purified bacterial proteins in vitro, and IFN-gamma responses were analyzed by ELISPOT and flow cytometry. Findings: B. pseudomallei was a potent activator of human peripheral blood NK cells for innate production of IFN-gamma. In addition, healthy individuals with serological evidence of exposure to B. pseudomallei and patients recovered from active melioidosis developed CD4(+) (and CD8(+)) T cells that recognized whole bacteria and purified proteins LolC, OppA, and PotF, members of the B. pseudomallei ABC transporter family. This response was primarily mediated by terminally differentiated T cells of the effector-memory (T(EMRA)) phenotype and correlated with the titer of anti-B. pseudomallei antibodies in the serum. Conclusions: Individuals living in a melioidosis-endemic region show clear evidence of T cell priming for the ability to make IFN-gamma that correlates with their serological status. The ability to detect T cell responses to defined B. pseudomallei proteins in large numbers of individuals now provides the opportunity to screen candidate antigens for inclusion in protein or polysaccharide-conjugate subunit vaccines against this important but neglected disease.

Published
2009

27. Plague

Author

Oyston, Petra C. F., Titball, Richard W., Lutwick, Suzanne M., editor, and Lutwick, Larry I., editor

Published
2009
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29. Is Clostridium perfringens epsilon toxin associated with multiple sclerosis?

Author

Titball, Richard W, Lewis, Nicholas, and Nicholas, Richard

Subjects
*CLOSTRIDIUM perfringens, *CLOSTRIDIA, *MULTIPLE sclerosis, *TOXINS, *CENTRAL nervous system, *PROTEIN receptors
Abstract

Clostridium perfringens epsilon toxin is associated with enterotoxaemia in livestock. More recently, it is proposed to play a role in multiple sclerosis (MS) in humans. Compared to matched controls, strains of C. perfringens which produce epsilon toxin are significantly more likely to be isolated from the gut of MS patients and at significantly higher levels; similarly, sera from MS patients are significantly more likely to contain antibodies to epsilon toxin. Epsilon toxin recognises the myelin and lymphocyte (MAL) protein receptor, damaging the blood–brain barrier and brain cells expressing MAL. In the experimental autoimmune encephalomyelitis model of MS, the toxin enables infiltration of immune cells into the central nervous system, inducing an MS-like disease. These studies provide evidence that epsilon toxin plays a role in MS, but do not yet fulfil Koch's postulates in proving a causal role. [ABSTRACT FROM AUTHOR]

Published
2023
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33. Exploiting the Burkholderia pseudomallei Acute Phase Antigen BPSL2765 for Structure-Based Epitope Discovery/Design in Structural Vaccinology

Author

Gourlay, Louise J., Peri, Claudio, Ferrer-Navarro, Mario, Conchillo-Solé, Oscar, Gori, Alessandro, Rinchai, Darawan, Thomas, Rachael J., Champion, Olivia L., Michell, Stephen L., Kewcharoenwong, Chidchamai, Nithichanon, Arnone, Lassaux, Patricia, Perletti, Lucia, Longhi, Renato, Lertmemongkolchai, Ganjana, Titball, Richard. W., Daura, Xavier, Colombo, Giorgio, and Bolognesi, Martino

Published
2013
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37. Second and Third Generation Plague Vaccines

Author

Titball, Richard W., Williamson, E. Diane, Back, Nathan, editor, Cohen, Irun R., editor, Kritchevsky, David, editor, Lajtha, Abel, editor, Paoletti, Rodolfo, editor, Skurnik, Mikael, editor, Bengoechea, José Antonio, editor, and Granfors, Kaisa, editor

Published
2003
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39. Signature-tagged Mutagenesis of Yersinia pestis

Author

Oyston, Petra C.F., Karlyshev, Andrey V., Wren, Brendan W., Titball, Richard W., Back, Nathan, editor, Cohen, Irun R., editor, Kritchevsky, David, editor, Lajtha, Abel, editor, Paoletti, Rodolfo, editor, Skurnik, Mikael, editor, Bengoechea, José Antonio, editor, and Granfors, Kaisa, editor

Published
2003
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40. DNA Adenine Methylation

Author

Taylor, Victoria L., Oyston, Petra C. F., Titball, Richard W., Back, Nathan, editor, Cohen, Irun R., editor, Kritchevsky, David, editor, Lajtha, Abel, editor, Paoletti, Rodolfo, editor, Skurnik, Mikael, editor, Bengoechea, José Antonio, editor, and Granfors, Kaisa, editor

Published
2003
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43. A Burkholderia pseudomallei Toxin Inhibits Helicase Activity of Translation Factor elF4A

Author

Cruz-Migoni, Abimael, Hautbergue, Guillaume M., Artymiuk, Peter J., Baker, Patrick J., Bokori-Brown, Monika, Chang, Chung-Te, Dickman, Mark J., Essex-Lopresti, Angela, Harding, Sarah V., Mahadi, Nor Muhammad, Marshall, Laura E., Mobbs, George W., Mohamed, Rahmah, Nathan, Sheila, Ngugi, Sarah A., Ong, Catherine, Ooi, Wen Fong, Partridge, Lynda J., Phillips, Helen L., Raih, M. Firdaus, Ruzheinikov, Sergei, Sarkar-Tyson, Mitali, Sedelnikova, Svetlana E., Smither, Sophie J., Tan, Patrick, Titball, Richard W., Wilson, Stuart A., and Rice, David W.

Published
2011

44. A bacterial process for selenium nanosphere assembly

Author

Debieux, Charles M., Dridge, Elizabeth J., Mueller, Claudia M., Splatt, Peter, Paszkiewicz, Konrad, Knight, Iona, Florance, Hannah, Love, John, Titball, Richard W., Lewis, Richard J., Richardson, David J., and Butler, Clive S.

Published
2011

48. A Burkholderia Pseudomallei Protein Microarray Reveals Serodiagnostic and Cross-Reactive Antigens

Author

Felgner, Philip L., Kayala, Matthew A., Vigil, Adam, Burk, Chad, Nakajima-Sasaki, Rie, Pablo, Jozelyn, Molina, Douglas M., Hirst, Siddiqua, Chew, Janet S. W., Wang, Dongling, Tan, Gladys, Duffield, Melanie, Yang, Ron, Neel, Julien, Chantratita, Narisara, Bancroft, Greg, Lertmemongkolchai, Ganjana, Davies, D. Huw, Baldi, Pierre, Peacock, Sharon, Titball, Richard W., and Palese, Peter

Published
2009
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