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Journal of Clinical Microbiology, April 2007, p. 1374-1375, Vol. 45, No. 4
0095-1137/07/$08.00+0     doi:10.1128/JCM.00076-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

LETTER TO THE EDITOR

The Operon Encoding SubAB, a Novel Cytotoxin, Is Present in Shiga toxin-producing Escherichia coli Isolates from the United States{triangledown}


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LETTER
 
Diarrhea-associated hemolytic uremic syndrome (D+HUS) is thought to result from endothelial cell damage following gastrointestinal infection with Shiga toxin-producing Escherichia coli (STEC) (10); Shiga toxin (Stx) is regarded as the main virulence factor causing these microangiopathic sequelae (1, 5). Since STEC species differ in their abilities to cause severe disease, other virulence factors may contribute to endothelial damage (1). It has been hypothesized that the recently discovered AB5 toxin subtilase cytotoxin (SubAB) may be one of these factors (1). Because of the separate modes of action of SubAB and Shiga toxins, the potential for cointeractions exists (4, 6).

SubAB was first isolated from an Australian non-O157 STEC strain 98NK2, associated with an outbreak of HUS in children (8). In mice, parenteral SubAB causes microangiopathy, suggesting a direct role in endothelial damage (7, 8). An estimated 10% of Australian STEC clinical isolates carry the subAB operon; in these strains, its presence is associated with stx2 and with the ehxA gene (7). Furthermore, these strains lack the eae gene encoding the outer membrane adhesion intimin encoded in the locus of the enterocyte effacement pathogenicity island. The global distribution of SubAB-encoding STEC strains is unknown. Although the epidemiology of D+HUS in Australia differs from that in the United States, with non-O157 STEC implicated more frequently in Australia, we hypothesized that STEC strains from the United States also contain the subAB operon.

STEC strains originating from sources in the United States were selected from two well-characterized, previously described strain collections (2, 9). Previously published multiplex PCR data for stx1, stx2, eae, and ehxA and serogroup/type information were used to select representative strains, allowing assessment of potential associations between the subAB operon and these virulence factors and different O serogroups. Three colonies were assessed in independent PCR runs to ensure correct strain classification, using 98NK2 as a positive control and two nonpathogenic E. coli laboratory strains, HB101 and XLI-Blue, as negative controls.

Table 1 shows that STEC strains of diverse origins from the United States harbor subA, confirming that SubAB-expressing organisms are present on the North American subcontinent. Of 46 isolates tested, 10 strains were subA positive: 6 from cattle, 3 from diarrhea patients, and 1 from an environmental water source. Furthermore, these strains have a virulence gene profile similar to that of subA-positive strains from Australia; 9 of 10 STEC strains from the United States that tested positive for subA had the gene encoding the stx2 toxin variant only, all were eae negative, and all were ehxA positive. Only one subA-positive STEC strain from the United States was positive for both stx1 and stx2. None of the 22 eae-positive strains had subA. Table 2 summarizes these results. Since these strains were specifically selected to represent different serogroups and virulence markers, no conclusions regarding the overall prevalence of SubAB in the United States can be drawn.


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  		TABLE 1. Presence of subA and other putative virulence genes in STEC strainsa


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  		TABLE 2. Summary of virulence factor coexpression of subA-positive and subA-negative STEC isolates

A potential association between the SubAB cytotoxin and human disease has not yet been studied. In the United States, non-O157 E. coli bacteria account for up to 20% to 50% of all STEC infections (3) and can cause HUS and hemorrhagic colitis. Thus, epidemiologic studies should be undertaken to assess a potential role for SubAB in contributing to microangiopathic sequelae following infection with these organisms. It would also be of interest to determine whether SubAB is present in strains from countries where non-0157 STEC predominates, such as Argentina, where the HUS prevalence is the highest in the world.


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FOOTNOTES
 
{triangledown} Published ahead of print on 7 February 2007. Back


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REFERENCES
 
    1
  1. Bielaszewska, M., and H. Karch. 2005. Consequences of enterohemorrhagic E. coli infection for the vascular epithelium. Thromb. Haemost. 94:312-318.[Medline]
    2. 2
  2. Hurley, B., C. Thorpe, and D. Acheson. 2001. Shiga toxin translocation across intestinal epithelial cells is enhanced by neutrophil transmigration. Infect. Immun. 69:6148-6155.[Abstract/Free Full Text]
    3. 3
  3. Johnson, K., C. Thorpe, and C. Sears. 2006. The emerging clinical importance of non-O157 Shiga toxin-producing Escherichia coli. Clin. Infect. Dis. 43:1587-1595.[CrossRef][Medline]
    4. 4
  4. Montecucco, C., and M. Molinari. 2006. Death of a chaperone. Nature 443:511-512.[CrossRef][Medline]
    5. 5
  5. Nataro, J. P., and J. B. Kaper. 1998. Diarrheagenic Escherichia coli. Clin. Microbiol. Rev. 11:142-201.[Abstract/Free Full Text]
    6. 6
  6. Paton, A., T. Beddoe, C. M. Thorpe, J. Whisstock, M. Wilce, J. Rossjohn, U. Talbot, and J. Paton. 2006. AB5 subtilase cytotoxin inactivates the endoplasmic reticulum chaperone BiP. Nature 443:548-552.[CrossRef][Medline]
    7. 7
  7. Paton, A., and J. Paton. 2005. Multiplex PCR for direct detection of Shiga toxigenic Escherichia coli strains producing the novel subtilase cytotoxin. J. Clin. Microbiol. 43:2944-2947.[Abstract/Free Full Text]
    8. 8
  8. Paton, A., P. Srimanote, U. Talbot, H. Wang, and J. Paton. 2004. A new family of potent AB5 cytotoxins produced by Shiga toxigenic Escherichia coli. J. Exp. Med. 200:35-46.[Abstract/Free Full Text]
    9. 9
  9. Ritchie, J., P. Wagner, D. Acheson, and M. Waldor. 2003. Comparison of Shiga toxin production by hemolytic-uremic syndrome-associated and bovine-associated Shiga toxin-producing Escherichia coli isolates. Appl. Environ. Microbiol. 69:1059-1066.[Abstract/Free Full Text]
    10. 10
  10. Thorpe, C. 2004. Shiga toxin-producing Escherichia coli infection. Clin. Infect. Dis. 38:1298-1303.[CrossRef][Medline]
A. Khaitan
D. M. Jandhyala
C. M. Thorpe*
Tufts—New England Medical Center
750 Washington Street, Box 041
Boston, Massachusetts 02111

J. M. Ritchie
Tufts University School of Medicine
Boston, Massachusetts 02111

A. W. Paton
University of Adelaide
Adelaide, South Australia

* Phone: (617) 636-0245, Fax: (617) 636-5292, E-mail: cthorpe{at}tufts-nemc.org

Journal of Clinical Microbiology, April 2007, p. 1374-1375, Vol. 45, No. 4
0095-1137/07/$08.00+0     doi:10.1128/JCM.00076-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.




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