Can colibactin (colibactin-producing Escherichia coli) bacteria be tested for?

Testing for Colibactin-Producing Bacteria

Currently, there are no standardized clinical tests specifically designed for detecting colibactin-producing bacteria in routine clinical practice. While colibactin is a genotoxin produced by certain strains of Escherichia coli that has been associated with colorectal cancer, testing for it remains primarily in the research domain rather than clinical diagnostics.

Current Testing Approaches for E. coli

Standard Clinical Testing Methods

• Clinical laboratories typically test for pathogenic E. coli using culture-based methods and tests for Shiga toxin, not colibactin 1
• The ideal specimen for E. coli testing is diarrheal stool collected as soon as possible after symptom onset, before antibiotic administration 1
• Standard testing includes:
  • Culture on selective media such as sorbitol-MacConkey agar (SMAC) 1
  • Enzyme immunoassay (EIA) for Shiga toxin detection 1
  • PCR-based methods for detecting virulence genes in specialized settings 1

Research Methods for Colibactin Detection

• Detection of colibactin-producing E. coli in research settings typically involves:
  • PCR targeting the polyketide synthase (pks) genomic island genes, particularly clbA and clbQ 2, 3
  • These tests are not FDA-approved for clinical diagnosis 1
  • Research studies have found higher prevalence of pks+ E. coli in colorectal cancer patients (16.7%) compared to healthy controls (4.3%) 2

Limitations of Current Testing

• Colibactin itself has been difficult to isolate and characterize due to its complex structure 4
• DNA-based detection methods for colibactin genes are not currently approved by FDA for human diagnostic use 1
• Commercial PCR kits that might detect colibactin-related genes are labeled for research use only 1
• Clinical laboratories considering DNA-based assays would need to establish performance specifications as required by CLIA 1

Special Considerations

• Patients with inflammatory bowel disease (IBD) have higher levels of colibactin-producing bacteria in their intestines and may be at increased risk for colorectal cancer 5
• Colibactin-producing E. coli are often from the B2 phylogenetic group, which has been associated with more aggressive cases of colorectal cancer 3
• In research settings, cytotoxicity assays using cell lines (such as HEK cells) can be used to assess the potential virulence of colibactin-producing E. coli isolates 3

Clinical Implications

• While research suggests a correlation between colibactin-producing bacteria and colorectal cancer, routine testing for these bacteria is not currently part of clinical practice 6, 2
• For patients with suspected pathogenic E. coli infection, standard testing for Shiga toxin-producing E. coli (STEC) remains the recommended approach 1
• Specialized testing for colibactin would typically be performed in research settings or by public health laboratories during specific investigations 1

Common Pitfalls

• Specimens for E. coli testing should be processed promptly; they should not be held for >24 hours unpreserved or >48 hours in transport medium 1
• Direct testing of stool for toxins is less sensitive than testing growth from broth culture or primary isolation media 1
• PCR assays on DNA extracted directly from whole stool specimens have low sensitivity and are not recommended 1