Home | Help | Feedback | Subscriptions | Archive | Search | Latest Articles

This Article Full Text Full Text (PDF, 325K) PPT slides of all figures Correction (v200,p1525) Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Paton, A. W. Articles by Paton, J. C. Search for Related Content PubMed PubMed Citation Articles by Paton, A. W. Articles by Paton, J. C. Social Bookmarking                            What's this?

A New Family of Potent AB₅ Cytotoxins Produced by Shiga Toxigenic Escherichia coli

Adrienne W. Paton, Potjanee Srimanote, Ursula M. Talbot, Hui Wang, and James C. Paton

School of Molecular and Biomedical Science, University of Adelaide, South Australia, 5005, Australia

Address correspondence to James C. Paton, School of Molecular and Biomedical Science, University of Adelaide, South Australia, 5005, Australia. Phone: 61-8-83035929; Fax: 61-8-83033262; email: james.paton{at}adelaide.edu.au

The Shiga toxigenic Escherichia coli (STEC) O113:H21 strain 98NK2, which was responsible for an outbreak of hemolytic uremic syndrome, secretes a highly potent and lethal subtilase cytotoxin that is unrelated to any bacterial toxin described to date. It is the prototype of a new family of AB₅ toxins, comprising a single 35-kilodalton (kD) A subunit and a pentamer of 13-kD B subunits. The A subunit is a subtilase-like serine protease distantly related to the BA_2875 gene product of Bacillus anthracis. The B subunit is related to a putative exported protein from Yersinia pestis, and binds to a mimic of the ganglioside GM2. Subtilase cytotoxin is encoded by two closely linked, cotranscribed genes (subA and subB), which, in strain 98NK2, are located on a large, conjugative virulence plasmid. Homologues of the genes are present in 32 out of 68 other STEC strains tested. Intraperitoneal injection of purified subtilase cytotoxin was fatal for mice and resulted in extensive microvascular thrombosis, as well as necrosis in the brain, kidneys, and liver. Oral challenge of mice with E. coli K-12–expressing cloned subA and subB resulted in dramatic weight loss. These findings suggest that the toxin may contribute to the pathogenesis of human disease.

Key Words: subtilase • enterohemorrhagic E. coli • serine protease • hemolytic uremic syndrome • microvascular thrombosis

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

• Buchkovich, N. J., Maguire, T. G., Paton, A. W., Paton, J. C., Alwine, J. C. (2009). The Endoplasmic Reticulum Chaperone BiP/GRP78 Is Important in the Structure and Function of the Human Cytomegalovirus Assembly Compartment. J. Virol. 83: 11421-11428 [Abstract] [Full Text]  
• Hu, C.-C. A., Dougan, S. K., Winter, S. V., Paton, A. W., Paton, J. C., Ploegh, H. L. (2009). Subtilase cytotoxin cleaves newly synthesized BiP and blocks antibody secretion in B lymphocytes. JEM 206: 2429-2440 [Abstract] [Full Text]  
• Slanec, T., Fruth, A., Creuzburg, K., Schmidt, H. (2009). Molecular Analysis of Virulence Profiles and Shiga Toxin Genes in Food-Borne Shiga Toxin-Producing Escherichia coli. Appl. Environ. Microbiol. 75: 6187-6197 [Abstract] [Full Text]  
• Wolfson, J. J., Jandhyala, D. M., Gorczyca, L. A., Qadeer, Z., Manning, S. D., Hadler, J., Rudrik, J. T., Thorpe, C. M. (2009). Prevalence of the Operon Encoding Subtilase Cytotoxin in Non-O157 Shiga Toxin-Producing Escherichia coli Isolated from Humans in the United States. J. Clin. Microbiol. 47: 3058-3059 [Full Text]  
• Herold, S., Paton, J. C., Paton, A. W. (2009). Sab, a Novel Autotransporter of Locus of Enterocyte Effacement-Negative Shiga-Toxigenic Escherichia coli O113:H21, Contributes to Adherence and Biofilm Formation. Infect. Immun. 77: 3234-3243 [Abstract] [Full Text]  
• Harama, D., Koyama, K., Mukai, M., Shimokawa, N., Miyata, M., Nakamura, Y., Ohnuma, Y., Ogawa, H., Matsuoka, S., Paton, A. W., Paton, J. C., Kitamura, M., Nakao, A. (2009). A Subcytotoxic Dose of Subtilase Cytotoxin Prevents Lipopolysaccharide-Induced Inflammatory Responses, Depending on its Capacity to Induce the Unfolded Protein Response. J. Immunol. 183: 1368-1374 [Abstract] [Full Text]  
• Yamazaki, H., Hiramatsu, N., Hayakawa, K., Tagawa, Y., Okamura, M., Ogata, R., Huang, T., Nakajima, S., Yao, J., Paton, A. W., Paton, J. C., Kitamura, M. (2009). Activation of the Akt-NF-{kappa}B Pathway by Subtilase Cytotoxin through the ATF6 Branch of the Unfolded Protein Response. J. Immunol. 183: 1480-1487 [Abstract] [Full Text]  
• Matsuura, G., Morinaga, N., Yahiro, K., Komine, R., Moss, J., Yoshida, H., Noda, M. (2009). Novel Subtilase Cytotoxin Produced by Shiga-Toxigenic Escherichia coli Induces Apoptosis in Vero Cells via Mitochondrial Membrane Damage. Infect. Immun. 77: 2919-2924 [Abstract] [Full Text]  
• Bielaszewska, M., Stoewe, F., Fruth, A., Zhang, W., Prager, R., Brockmeyer, J., Mellmann, A., Karch, H., Friedrich, A. W. (2009). Shiga Toxin, Cytolethal Distending Toxin, and Hemolysin Repertoires in Clinical Escherichia coli O91 Isolates. J. Clin. Microbiol. 47: 2061-2066 [Abstract] [Full Text]  
• Bielaszewska, M., Prager, R., Vandivinit, L., Musken, A., Mellmann, A., Holt, N. J., Tarr, P. I., Karch, H., Zhang, W. (2009). Detection and Characterization of the Fimbrial sfp Cluster in Enterohemorrhagic Escherichia coli O165:H25/NM Isolates from Humans and Cattle. Appl. Environ. Microbiol. 75: 64-71 [Abstract] [Full Text]  
• Buchkovich, N. J., Maguire, T. G., Yu, Y., Paton, A. W., Paton, J. C., Alwine, J. C. (2008). Human Cytomegalovirus Specifically Controls the Levels of the Endoplasmic Reticulum Chaperone BiP/GRP78, Which Is Required for Virion Assembly. J. Virol. 82: 31-39 [Abstract] [Full Text]  
• Khaitan, A., Jandhyala, D. M., Thorpe, C. M., Ritchie, J. M., Paton, A. W. (2007). The Operon Encoding SubAB, a Novel Cytotoxin, Is Present in Shiga toxin-producing Escherichia coli Isolates from the United States. J. Clin. Microbiol. 45: 1374-1375 [Full Text]  
• Gyles, C. L. (2007). Shiga toxin-producing Escherichia coli: An overview. J ANIM SCI 85: E45-E62 [Abstract] [Full Text]  
• Morinaga, N., Yahiro, K., Matsuura, G., Watanabe, M., Nomura, F., Moss, J., Noda, M. (2007). Two Distinct Cytotoxic Activities of Subtilase Cytotoxin Produced by Shiga-Toxigenic Escherichia coli. Infect. Immun. 75: 488-496 [Abstract] [Full Text]  
• Sonntag, A.-K., Bielaszewska, M., Mellmann, A., Dierksen, N., Schierack, P., Wieler, L. H., Schmidt, M. A., Karch, H. (2005). Shiga Toxin 2e-Producing Escherichia coli Isolates from Humans and Pigs Differ in Their Virulence Profiles and Interactions with Intestinal Epithelial Cells. Appl. Environ. Microbiol. 71: 8855-8863 [Abstract] [Full Text]  
• Talbot, U. M., Paton, J. C., Paton, A. W. (2005). Protective Immunization of Mice with an Active-Site Mutant of Subtilase Cytotoxin of Shiga Toxin-Producing Escherichia coli. Infect. Immun. 73: 4432-4436 [Abstract] [Full Text]  
• Paton, A. W., Paton, J. C. (2005). Multiplex PCR for Direct Detection of Shiga Toxigenic Escherichia coli Strains Producing the Novel Subtilase Cytotoxin. J. Clin. Microbiol. 43: 2944-2947 [Abstract] [Full Text]  
• Noris, M., Remuzzi, G. (2005). Hemolytic Uremic Syndrome. J. Am. Soc. Nephrol. 16: 1035-1050 [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search