Do Shiga Toxin-producing Escherichia coli (STEC) strains possess the Locus of Enterocyte Effacement (LEE) pathogenicity island?

Presence of LEE Pathogenicity Island in STEC Strains

Not all Shiga toxin-producing Escherichia coli (STEC) strains possess the Locus of Enterocyte Effacement (LEE) pathogenicity island; O157 STEC strains almost universally contain LEE, while many non-O157 STEC strains are LEE-negative. 1, 2

STEC Classification Based on LEE Status

LEE-Positive STEC

• O157 STEC strains, which are responsible for most STEC outbreaks and severe disease cases, almost universally contain the LEE pathogenicity island 1
• LEE encodes genes that mediate colonization of the human intestine, including the eae gene 1, 2
• The presence of both stx2 and eae genes (found in LEE) is associated with increased risk of severe disease, including hemolytic uremic syndrome (HUS) 1, 3

LEE-Negative STEC

• An emerging subset of STEC strains lacks the LEE pathogenicity island but can still cause severe disease 2, 4
• LEE-negative STEC strains have been increasingly associated with human disease in several countries 2
• These strains utilize alternative adherence mechanisms, including:
  • Locus of Adhesion and Autoaggregation (LAA) - an 86-kb pathogenicity island found exclusively in emerging LEE-negative STEC strains 2, 5
  • LAA contains 80 genes encoding novel and known virulence factors associated with adherence and autoaggregation 2
  • LAA is found in approximately 46% of LEE-negative STEC strains, particularly those belonging to serogroups O91, O174, O113, O171, O178, and O130 5

Clinical and Diagnostic Implications

Virulence Assessment

• The presence of stx2 and eae (LEE) genes is associated with increased risk of severe disease 1, 3
• LEE-negative STEC strains harboring LAA have been linked to severe disease, including HUS cases 2, 5
• The CDC recommends laboratory methods that can detect both LEE-positive and LEE-negative STEC strains 1, 3

Laboratory Detection

• Simultaneous testing for O157 STEC (typically LEE-positive) and non-O157 STEC (which may be LEE-negative) is recommended 1
• Detection methods should include:
  • Culture for E. coli O157:H7 using selective media
  • Testing for Shiga toxin production (EIA)
  • PCR for detecting stx1 and stx2 genes 3
• Future diagnostic methods should ideally assess virulence potential by detecting genes like stx2 and eae 1

Evolutionary Context

• LEE-positive STEC evolved from enteropathogenic E. coli (EPEC) 4
• LEE-negative STEC with LAA represent a more recent evolutionary event 2
• The acquisition of LAA appears to be a recent evolutionary development contributing to the emergence of virulent LEE-negative STEC strains 2, 5
• LAA is predominantly found in STEC strains belonging to phylogroup B1 (91%) 5

Important Considerations

• When assessing STEC virulence potential, testing for both LEE (eae gene) and Shiga toxin genes is crucial 1, 3
• The presence of LAA in LEE-negative STEC may serve as a marker for potentially virulent strains 2, 5
• Both LEE-positive and LEE-negative STEC strains can cause severe disease, though the molecular mechanisms differ 2, 4
• The six most common non-O157 EHEC serogroups in the United States (O26, O45, O103, O111, O121, and O145) may include both LEE-positive and LEE-negative strains 3