Colibactin possessing E. coli isolates in association with colorectal cancer and their genetic diversity among Pakistani population
Open accessAbstract
Colorectal cancer (CRC) is the third most prevalent cause of tumorigenesis and several pathogenic bacteria have been correlated with aggressive cases of cancer i.e., genotoxin (colibactin) producing Escherichia coli ( E . coli) . This study was designed to investigate the genetic diversity of clb + clb + E . coli strains and their association with CRC. Pathogenic E . coli isolates from colorectal biopsies were characterized based on phylotypes, antibiotic resistance pattern, and (Enterobacterial Repetitive Intergenic Consensus Sequence-based Polymerase Chain Reaction) ERIC-PCR. Furthermore, isolates were screened for the presence of the Pks (polyketide synthase) Island specifically targeting colibactin genes A and Q. The selective clb + clb + isolates were subjected to cytotoxicity assay using Human embryonic kidney (HEK) cell lines. We revealed that 43.47% of the cancer-associated E . coli isolates were from phylogroup B2 comparatively more pathogenic than rest while in the case of healthy controls no isolate was found from B2. Moreover, 90% were found positive for colibactin and pks (polyketide synthase) island, while none of the healthy controls were found positive for colibactin genes. All healthy and cancer-associated isolates were tested against 15 antibiotic agents, we observed that cancer-associated isolates showed a wide range of resistance from 96% against Nalidixic acid to 48% against Doxycycline. Moreover, E . coli isolates were further genotyped using ERIC-PCR, and selected clb + clb + E . coli isolates were subjected to cytotoxicity assay. We recorded the significant cytotoxic activity of clb+clb+ E . coli phylogroup B2 isolates that might have contributed towards the progression of CRC or dysbiosis of healthy gut microbiota protecting against CRC pathogenesis. Our results revealed a significant p <0.023 association of dietary habits and hygiene p <0.001with CRC. This is the first study to report the prevalence of E . coli phylogroups and the role of colibactin most virulent phylogroup B2 among Pakistani individuals from low socioeconomic setup.
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The B2 phylotype is likely the colibactin-positive most virulent phylogroup among E. coli.
“the B2 phylotype is likely the colibactin-positive most virulent phylogroup among E. coli [145].”
From Selection, Comparative Genomics, and Potential Probiotic Features of Escherichia coli 5C, a pks-Negative Strain Isolated from Healthy Infant Donor Feces (2026) · cites this paper as [145]
The Abstract describes B2 isolates from colorectal cancer patients as comparatively more pathogenic than the rest. The Results and discussion section on colibactin genes reports that all B2 isolates from those patients tested positive, while the other cancer-associated isolates did not. These findings support the claim for the studied isolates, but do not establish B2 as the most virulent phylogroup among E. coli generally. (LLM, conf=0.84)
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“…each other phylogenetically among E. coli sensu stricto [107]; that strains responsible for extra-intestinal infection were far more likely to be members of phylogroups B2 than A [143, 144]; and that the B2 phylotype is likely the colibactin-positive most virulent phylogroup among E. coli [145].”
- Authors
- Tariq, H., Noreen, Z., Ahmad, A., Khan, L., Ali, M., Malik, M., Javed, A., Rasheed, F., Fatima, A., Kocagoz, T., Sezerman, U., & Bokhari, H.
- Affiliations
- COMSATS University Islamabad (PK)
- Pakistan Institute of Medical Sciences (PK)
- National University of Sciences and Technology (PK)
- Quaid-i-Azam University (PK)
- Corresponding author
- Bokhari, Habib
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2022-11-11
- Volume
- 17
- Issue
- 11
- Pages
- e0262662
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC9651576
- OpenAlex
- W4308791422
- Cited by
- 22
- References
- 32
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 8 · 2023: 1
- FWCI
- 2.52
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- PROJECT NO.PSF-TUBITAK/C-COMSATS
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Escherichia coli research studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Antibiotic Resistance in Bacteria
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Enterobacteriaceae and Cronobacter Research
- Keywords
- colibactin, Escherichia coli, colorectal cancer, phylogroup B2, antibiotic resistance, ERIC-PCR genotyping, cytotoxicity, gut dysbiosis, dietary habits, hygiene, Pakistani population
- MeSH terms
- Escherichia coli, Escherichia coli Infections, Humans, Pakistan, Peptides, Genetic Variation, Colorectal Neoplasms, Polyketide Synthases, Polyketides
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