Can non-O157 (Escherichia coli) variants with the Shiga toxin (stx) gene still cause Enterohemorrhagic Escherichia coli (EHEC)?

Non-O157 E. coli Variants with stx Gene Can Cause EHEC

Yes, non-O157 E. coli variants that possess the Shiga toxin (stx) gene can definitely cause Enterohemorrhagic Escherichia coli (EHEC) infections. 1 These non-O157 STEC strains can produce the same severe clinical manifestations as O157 strains, including hemorrhagic colitis and hemolytic uremic syndrome (HUS).

Characteristics of Non-O157 EHEC

• At least 150 STEC serotypes have been associated with human disease 1

• The six most common non-O157 EHEC serogroups in the United States are:

  • O26
  • O45
  • O103
  • O111
  • O121
  • O145 1

• Non-O157 STEC strains that produce only Stx2 are more often associated with HUS than strains that produce only Stx1 or both Stx1 and Stx2 2

Virulence Factors in Non-O157 EHEC

The key virulence factors that define EHEC, regardless of serotype, include:

1. Shiga toxin genes (stx1 and/or stx2): These are the primary virulence determinants 3

   • Non-O157 strains more commonly carry stx1 (99% versus 1% in O157 strains) 4
   • O157 strains more frequently carry stx2 with stx2c (64% versus 2% in non-O157 strains) 4

2. Intimin gene (eae): Enables intimate attachment to intestinal epithelial cells 5

   • Present in both O157 and non-O157 EHEC strains
   • Responsible for the attaching and effacing (A/E) lesion characteristic of EHEC 3

3. EHEC-hemolysin gene (EHEC-hlyA): Another important virulence marker 5

   • Found in most clinical EHEC isolates regardless of serotype

Diagnostic Considerations

The CDC and MMWR guidelines recommend:

1. All stools from patients with acute community-acquired diarrhea should be tested for both:

   • O157 STEC through culture on selective media
   • Shiga toxins or their genes through EIA or PCR 2, 1

2. Laboratory identification methods:

   • Culture for E. coli O157:H7 using selective media like SMAC
   • EIA for detecting Shiga toxin
   • PCR for detecting stx1 and stx2 genes 1

3. Isolation of non-O157 STEC:

   • Streak Shiga toxin-positive broth to less selective agar (MacConkey, SMAC, SSI enteric medium, or blood agar)
   • Test colonies for Shiga toxin production by EIA or for stx1/stx2 genes by PCR
   • Test using O-specific antisera for common STEC-associated O antigens 2

Clinical Implications

• Non-O157 STEC with stx genes can cause the full spectrum of EHEC disease, including:

  • Mild diarrhea
  • Hemorrhagic colitis
  • Hemolytic uremic syndrome (HUS) 3

• Strains with the virulence profile that includes stx2 genes are more commonly associated with severe outcomes like HUS 4

• Early identification of both O157 and non-O157 STEC is crucial for:

  • Implementing appropriate management
  • Preventing complications
  • Initiating parenteral volume expansion early to potentially decrease renal damage 1

Evolutionary Perspective

According to the 'parallel evolution model', non-O157 EHECs have independently acquired the major virulence determinants (stx genes and LEE) through lateral gene transfer, particularly through bacteriophage infections 6. Despite belonging to distinct clonal lineages from O157, they share an unexpectedly large number of virulence genes that enable them to cause similar clinical manifestations 6.

Public Health Importance

• All STEC isolates, both O157 and non-O157, should be forwarded to public health laboratories for:

  • Confirmation of Shiga toxin production
  • Serogroup determination
  • PFGE subtyping 2
  • Molecular characterization 1

• This is essential for outbreak detection, investigation, and control measures 1

The presence of stx genes, particularly stx2, along with other virulence factors like eae and EHEC-hlyA, is what defines a strain as EHEC, regardless of whether it belongs to the O157 or non-O157 serogroup.