This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Alfa, M. J.
Right arrow Articles by Embil, J. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Alfa, M. J.
Right arrow Articles by Embil, J. M.

 Previous Article  |  Next Article 

Journal of Clinical Microbiology, July 2000, p. 2706-2714, Vol. 38, No. 7
0095-1137/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Characterization of a Toxin A-Negative, Toxin B-Positive Strain of Clostridium difficile Responsible for a Nosocomial Outbreak of Clostridium difficile-Associated Diarrhea

Michelle J. Alfa,1,2,* Amin Kabani,1,3 David Lyerly,4 Scott Moncrief,4 Laurie M. Neville,4 Ali Al-Barrak,3 Godfrey K. H. Harding,1,2,3 Brenda Dyck,5 Karen Olekson,5 and John M. Embil1,3,5

Department of Medical Microbiology1 and Department of Medicine,3 University of Manitoba, Microbiology, St. Boniface General Hospital,2 and Infection Control Health Sciences Centre,5 Winnipeg, Manitoba, Canada, and Techlab Inc., Blacksburg, Virginia4

Received 9 February 2000/Returned for modification 7 March 2000/Accepted 29 March 2000

Clostridium difficile-associated diarrhea (CAD) is a very common nosocomial infection that contributes significantly to patient morbidity and mortality as well as to the cost of hospitalization. Previously, strains of toxin A-negative, toxin B-positive C. difficile were not thought to be associated with clinically significant disease. This study reports the characterization of a toxin A-negative, toxin B-positive strain of C. difficile that was responsible for a recently described nosocomial outbreak of CAD. Analysis of the seven patient isolates from the outbreak by pulsed-field gel electrophoresis indicated that this outbreak was due to transmission of a single strain of C. difficile. Our characterization of this strain (HSC98) has demonstrated that the toxin A gene lacks 1.8 kb from the carboxy repetitive oligopeptide (CROP) region but apparently has no other major deletions from other regions of the toxin A or toxin B gene. The remaining 1.3-kb fragment of the toxin A CROP region from strain HSC98 showed 98% sequence homology with strain 1470, previously reported by M. Weidmann in 1997 (GenBank accession number Y12616), suggesting that HSC98 is toxinotype VIII. The HSC98 strain infecting patients involved in this outbreak produced the full spectrum of clinical illness usually associated with C. difficile-associated disease. This pathogenic spectrum was manifest despite the inability of this strain to alter tight junctions as determined by using in vitro tissue culture testing, which suggested that no functional toxin A was produced by this strain.

* Corresponding author. Mailing address: Microbiology, St. Boniface General Hospital, 409 Tache Ave., Winnipeg, Manitoba, Canada R2H 2A6. Phone: (204) 237-2105. Fax: (204) 237-7678. E-mail: malfa{at}cc.umanitoba.ca.

Journal of Clinical Microbiology, July 2000, p. 2706-2714, Vol. 38, No. 7
0095-1137/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Quesada-Gomez, C., Rodriguez, C., Gamboa-Coronado, M. d. M., Rodriguez-Cavallini, E., Du, T., Mulvey, M. R., Villalobos-Zuniga, M., Boza-Cordero, R. (2010). Emergence of Clostridium difficile NAP1 in Latin America. J. Clin. Microbiol. 48: 669-670 [Full Text]  
  • Larson, A. M., Fung, A. M., Fang, F. C. (2010). Evaluation of tcdB Real-Time PCR in a Three-Step Diagnostic Algorithm for Detection of Toxigenic Clostridium difficile. J. Clin. Microbiol. 48: 124-130 [Abstract] [Full Text]  
  • Shin, B.-M., Kuak, E. Y., Lee, E. J., Songer, J. G. (2009). Algorithm Combining Toxin Immunoassay and Stool Culture for Diagnosis of Clostridium difficile Infection. J. Clin. Microbiol. 47: 2952-2956 [Abstract] [Full Text]  
  • Janvilisri, T., Scaria, J., Thompson, A. D., Nicholson, A., Limbago, B. M., Arroyo, L. G., Songer, J. G., Grohn, Y. T., Chang, Y.-F. (2009). Microarray Identification of Clostridium difficile Core Components and Divergent Regions Associated with Host Origin. J. Bacteriol. 191: 3881-3891 [Abstract] [Full Text]  
  • Ochsner, U. A., Bell, S. J., O'Leary, A. L., Hoang, T., Stone, K. C., Young, C. L., Critchley, I. A., Janjic, N. (2009). Inhibitory effect of REP3123 on toxin and spore formation in Clostridium difficile, and in vivo efficacy in a hamster gastrointestinal infection model. J Antimicrob Chemother 63: 964-971 [Abstract] [Full Text]  
  • Monaghan, T, Boswell, T, Mahida, Y R (2009). Recent advances in Clostridium difficile-associated disease. Postgrad. Med. J. 85: 152-162 [Abstract] [Full Text]  
  • Martin, H., Willey, B., Low, D. E., Staempfli, H. R., McGeer, A., Boerlin, P., Mulvey, M., Weese, J. S. (2008). Characterization of Clostridium difficile Strains Isolated from Patients in Ontario, Canada, from 2004 to 2006. J. Clin. Microbiol. 46: 2999-3004 [Abstract] [Full Text]  
  • Shin, B.-M., Kuak, E. Y., Yoo, H. M., Kim, E. C., Lee, K., Kang, J.-O., Whang, D. H., Shin, J.-H. (2008). Multicentre study of the prevalence of toxigenic Clostridium difficile in Korea: results of a retrospective study 2000-2005. J Med Microbiol 57: 697-701 [Abstract] [Full Text]  
  • Monaghan, T, Boswell, T, Mahida, Y R (2008). Recent advances in Clostridium difficile-associated disease. Gut 57: 850-860 [Abstract] [Full Text]  
  • van den Berg, R. J., Schaap, I., Templeton, K. E., Klaassen, C. H. W., Kuijper, E. J. (2007). Typing and Subtyping of Clostridium difficile Isolates by Using Multiple-Locus Variable-Number Tandem-Repeat Analysis. J. Clin. Microbiol. 45: 1024-1028 [Abstract] [Full Text]  
  • Chae, S., Eckmann, L., Miyamoto, Y., Pothoulakis, C., Karin, M., Kagnoff, M. F. (2006). Epithelial Cell I{kappa}B-Kinase beta Has an Important Protective Role in Clostridium difficile Toxin A-Induced Mucosal Injury. J. Immunol. 177: 1214-1220 [Abstract] [Full Text]  
  • Pituch, H., Brazier, J. S., Obuch-Woszczatynski, P., Wultanska, D., Meisel-Mikolajczyk, F., Luczak, M. (2006). Prevalence and association of PCR ribotypes of Clostridium difficile isolated from symptomatic patients from Warsaw with macrolide-lincosamide-streptogramin B (MLSB) type resistance. J Med Microbiol 55: 207-213 [Abstract] [Full Text]  
  • Kato, H., Yokoyama, T., Kato, H., Arakawa, Y. (2005). Rapid and Simple Method for Detecting the Toxin B Gene of Clostridium difficile in Stool Specimens by Loop-Mediated Isothermal Amplification. J. Clin. Microbiol. 43: 6108-6112 [Abstract] [Full Text]  
  • Lemee, L., Bourgeois, I., Ruffin, E., Collignon, A., Lemeland, J.-F., Pons, J.-L. (2005). Multilocus sequence analysis and comparative evolution of virulence-associated genes and housekeeping genes of Clostridium difficile. Microbiology 151: 3171-3180 [Abstract] [Full Text]  
  • Voth, D. E., Ballard, J. D. (2005). Clostridium difficile Toxins: Mechanism of Action and Role in Disease. Clin. Microbiol. Rev. 18: 247-263 [Abstract] [Full Text]  
  • Pituch, H., Rupnik, M., Obuch-Woszczatynski, P., Grubesic, A., Meisel-Mikolajczyk, F., Luczak, M. (2005). Detection of binary-toxin genes (cdtA and cdtB) among Clostridium difficile strains isolated from patients with C. difficile-associated diarrhoea (CDAD) in Poland. J Med Microbiol 54: 143-147 [Abstract] [Full Text]  
  • Alonso, R, Martin, A, Pelaez, T, Marin, M, Rodriguez-Creixems, M, Bouza, E (2005). Toxigenic status of Clostridium difficile in a large Spanish teaching hospital. J Med Microbiol 54: 159-162 [Abstract] [Full Text]  
  • van den Berg, R. J, Ameen, H. A., Furusawa, T., Claas, E. C., van der Vorm, E. R, Kuijper, E. J (2005). Coexistence of multiple PCR-ribotype strains of Clostridium difficile in faecal samples limits epidemiological studies. J Med Microbiol 54: 173-179 [Abstract] [Full Text]  
  • Delmee, M., Van Broeck, J., Simon, A., Janssens, M., Avesani, V. (2005). Laboratory diagnosis of Clostridium difficile-associated diarrhoea: a plea for culture. J Med Microbiol 54: 187-191 [Abstract] [Full Text]  
  • Pituch, H., Kreft, D., Obuch-Woszczatynski, P., Wultanska, D., Meisel-Mikolajczyk, F., Luczak, M., van Belkum, A. (2005). Clonal Spread of a Clostridium difficile Strain with a Complete Set of Toxin A, Toxin B, and Binary Toxin Genes among Polish Patients with Clostridium difficile-Associated Diarrhea. J. Clin. Microbiol. 43: 472-475 [Abstract] [Full Text]  
  • Lemee, L., Dhalluin, A., Testelin, S., Mattrat, M.-A., Maillard, K., Lemeland, J.-F., Pons, J.-L. (2004). Multiplex PCR Targeting tpi (Triose Phosphate Isomerase), tcdA (Toxin A), and tcdB (Toxin B) Genes for Toxigenic Culture of Clostridium difficile. J. Clin. Microbiol. 42: 5710-5714 [Abstract] [Full Text]  
  • Spigaglia, P., Mastrantonio, P. (2004). Comparative analysis of Clostridium difficile clinical isolates belonging to different genetic lineages and time periods. J Med Microbiol 53: 1129-1136 [Abstract] [Full Text]  
  • Snell, H., Ramos, M., Longo, S., John, M., Hussain, Z. (2004). Performance of the TechLab C. DIFF CHEK-60 Enzyme Immunoassay (EIA) in Combination with the C. difficile Tox A/B II EIA Kit, the Triage C. difficile Panel Immunoassay, and a Cytotoxin Assay for Diagnosis of Clostridium difficile-Associated Diarrhea. J. Clin. Microbiol. 42: 4863-4865 [Abstract] [Full Text]  
  • Lemee, L., Dhalluin, A., Pestel-Caron, M., Lemeland, J.-F., Pons, J.-L. (2004). Multilocus Sequence Typing Analysis of Human and Animal Clostridium difficile Isolates of Various Toxigenic Types. J. Clin. Microbiol. 42: 2609-2617 [Abstract] [Full Text]  
  • van den Berg, R. J., Claas, E. C. J., Oyib, D. H., Klaassen, C. H. W., Dijkshoorn, L., Brazier, J. S., Kuijper, E. J. (2004). Characterization of Toxin A-Negative, Toxin B-Positive Clostridium difficile Isolates from Outbreaks in Different Countries by Amplified Fragment Length Polymorphism and PCR Ribotyping. J. Clin. Microbiol. 42: 1035-1041 [Abstract] [Full Text]  
  • Blake, J. E., Mitsikosta, F., Metcalfe, M. A. (2004). Immunological detection and cytotoxic properties of toxins from toxin A-positive, toxin B-positive Clostridium difficile variants. J Med Microbiol 53: 197-205 [Abstract] [Full Text]  
  • Geric, B., Johnson, S., Gerding, D. N., Grabnar, M., Rupnik, M. (2003). Frequency of Binary Toxin Genes among Clostridium difficile Strains That Do Not Produce Large Clostridial Toxins. J. Clin. Microbiol. 41: 5227-5232 [Abstract] [Full Text]  
  • Neunlist, M., Barouk, J., Michel, K., Just, I., Oreshkova, T., Schemann, M., Galmiche, J. P. (2003). Toxin B of Clostridium difficile activates human VIP submucosal neurons, in part via an IL-1{beta}-dependent pathway. Am. J. Physiol. Gastrointest. Liver Physiol. 285: G1049-G1055 [Abstract] [Full Text]  
  • Pituch, H., van Belkum, A., van den Braak, N., Obuch-Woszczatynski, P., Verbrugh, H., Meisel-Mikolajczyk, F., Luczak, M. (2003). Recent Emergence of an Epidemic Clindamycin-Resistant Clone of Clostridium difficile among Polish Patients with C. difficile-Associated Diarrhea. J. Clin. Microbiol. 41: 4184-4187 [Abstract] [Full Text]  
  • Johnson, S., Sambol, S. P., Brazier, J. S., Delmee, M., Avesani, V., Merrigan, M. M., Gerding, D. N. (2003). International Typing Study of Toxin A-Negative, Toxin B-Positive Clostridium difficile Variants. J. Clin. Microbiol. 41: 1543-1547 [Abstract] [Full Text]  
  • Rupnik, M., Kato, N., Grabnar, M., Kato, H. (2003). New Types of Toxin A-Negative, Toxin B-Positive Strains among Clostridium difficile Isolates from Asia. J. Clin. Microbiol. 41: 1118-1125 [Abstract] [Full Text]  
  • Wilkins, T. D., Lyerly, D. M. (2003). Clostridium difficile Testing: after 20 Years, Still Challenging. J. Clin. Microbiol. 41: 531-534 [Full Text]  
  • Turgeon, D. K., Novicki, T. J., Quick, J., Carlson, L., Miller, P., Ulness, B., Cent, A., Ashley, R., Larson, A., Coyle, M., Limaye, A. P., Cookson, B. T., Fritsche, T. R. (2003). Six Rapid Tests for Direct Detection of Clostridium difficile and Its Toxins in Fecal Samples Compared with the Fibroblast Cytotoxicity Assay. J. Clin. Microbiol. 41: 667-670 [Abstract] [Full Text]  
  • Spigaglia, P., Mastrantonio, P. (2002). Molecular Analysis of the Pathogenicity Locus and Polymorphism in the Putative Negative Regulator of Toxin Production (TcdC) among Clostridium difficile Clinical Isolates. J. Clin. Microbiol. 40: 3470-3475 [Abstract] [Full Text]  
  • Barbut, F., Lalande, V., Burghoffer, B., Thien, H. V., Grimprel, E., Petit, J.-C. (2002). Prevalence and Genetic Characterization of Toxin A Variant Strains of Clostridium difficile among Adults and Children with Diarrhea in France. J. Clin. Microbiol. 40: 2079-2083 [Abstract] [Full Text]  
  • Johnson, S., Kent, S. A., O'Leary, K. J., Merrigan, M. M., Sambol, S. P., Peterson, L. R., Gerding, D. N. (2001). Fatal Pseudomembranous Colitis Associated with a Variant Clostridium difficile Strain Not Detected by Toxin A Immunoassay. ANN INTERN MED 135: 434-438 [Abstract] [Full Text]  
  • O'Connor, D., Hynes, P., Cormican, M., Collins, E., Corbett-Feeney, G., Cassidy, M. (2001). Evaluation of Methods for Detection of Toxins in Specimens of Feces Submitted for Diagnosis of Clostridium difficile- Associated Diarrhea. J. Clin. Microbiol. 39: 2846-2849 [Abstract] [Full Text]  
  • Kato, H., Kato, N., Watanabe, K., Yamamoto, T., Suzuki, K., Ishigo, S., Kunihiro, S., Nakamura, I., Killgore, G. E., Nakamura, S. (2001). Analysis of Clostridium difficile Isolates from Nosocomial Outbreaks at Three Hospitals in Diverse Areas of Japan. J. Clin. Microbiol. 39: 1391-1395 [Abstract] [Full Text]  


Copyright © 2010 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»