COLIBACTIN-PRODUCING E. COLI AND ITS CORRELATION WITH COLORECTAL CANCER IN KAZAKHSTANI PATIENTS

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Authors

A.K. Surdeanu

Department of Biotechnology and Microbiology, L.N. Gumilyov Eurasian National University. Astana, Kazakhstan, 010000

B.A. Kurentay

LLP « National Center for Biotechnology», Korgalzhyn highway 13/5, Astana, Kazakhstan, 010000

A.D. Gusmaulemova

LLP « National Center for Biotechnology», Korgalzhyn highway 13/5, Astana, Kazakhstan, 010000

D.S. Bayanbek

LLP « National Center for Biotechnology», Korgalzhyn highway 13/5, Astana, Kazakhstan, 010000

G.N. Kulmambetova

LLP « National Center for Biotechnology», Korgalzhyn highway 13/5, Astana, Kazakhstan, 010000

Abstract

In recent years, increasing evidence has confirmed the importance of intestinal dysbiosis in the development and progression of colorectal cancer (CRC). Particular attention is paid to colibactin-producing Escherichia coli, which is considered one of the key microbial factors in carcinogenesis. Colibactin-producing Escherichia coli carries the pks pathogenicity island encoding the low-molecular genotoxin colibactin. This toxin has a pronounced cytotoxic effect on intestinal epithelial cells, causing double-strand DNA breaks and cell cycle arrest. Such damage contributes to the development of genomic instability, which ultimately increases the risk of colorectal cancer.

The aim of our study was to determine the clinical role of pks+ E. coli in the development and progression of CRC in Kazakhstani patients. Biopsies of the intestinal mucosa were obtained from 113 patients of the National Scientific Oncology Center with a confirmed diagnosis of colorectal adenocarcinoma from three sites (tumor, adjacent tumor-unaltered area, and distally located healthy area). To detect marker genes of colibactin (clbA, clbB, clbQ) in the selected biomaterial, quantitative PCR and routine PCR methods were used. A comprehensive assessment of the relationship between the carriage of pks+ Escherichia coli and such factors as tumor size and location, consumption of red and processed meat, the presence of bad habits, as well as metabolic and somatic diseases in patients was carried out.

Our results demonstrated that colibactin-producing E. coli was detected in 60% of tumor tissue biopsies, 53% of tumor-adjacent samples, and 54% of distal intestinal mucosa biopsies in cancer patients (P> 0.05). A statistically significant relationship was found between pks+ Escherichia coli carriage and tumor size in patients with CRC (P=0.009). This may indicate that pathogenic E. coli strains act not only as driver microorganisms initiating colon carcinogenesis, but also as potential long-term colonizers of tumor tissue involved in the pathogenesis and progression of the disease at later stages.

Keywords

Escherichia coli, pks , detection, colibactin, colorectal cancer, qPCR, tumor

Article Details

References

Pandey H., Tang D.W.T., Wong S.H. et al. Gut Microbiota in Colorectal Cancer: Biological Role and Therapeutic Opportunities // Cancers (Basel). ‒ 2023. ‒ Vol.15, №3.

Akinduti P.A., Izevbigie O.O., Akinduti O.A. et al. Fecal Carriage of Colibactin-Encoding Escherichia coli Associated With Colorectal Cancer Among a Student Populace // Open Forum Infect Dis. ‒ 2024. ‒ Vol.11, №4. ‒ P.ofae106.

Qin J., Li R., Raes J. et al. A human gut microbial gene catalogue established by metagenomic sequencing // Nature. ‒ 2010. ‒ Vol.464, №7285. ‒ P.59-65.

Neish A.S. Microbes in gastrointestinal health and disease // Gastroenterology. ‒ 2009. ‒ Vol.136, №1. ‒ P.65-80.

Jandhyala S.M., Talukdar R., Subramanyam C. et al. Role of the normal gut microbiota // World J Gastroenterol. ‒ 2015. ‒ Vol.21, №29. ‒ P.8787-8803.

Villéger R., Lopès A., Veziant J. et al. Microbial markers in colorectal cancer detection and/or prognosis // World J Gastroenterol. ‒ 2018. ‒ Vol.24, №22. ‒ P.2327-2347.

Tariq H., Noreen Z., Ahmad A. et al. Colibactin possessing E. coli isolates in association with colorectal cancer and their genetic diversity among Pakistani population // PLoS One. ‒ 2022. ‒ Vol.17, №11. ‒ P.e0262662.

Sadeghi M., Mestivier D., Sobhani I. Contribution of pks+ Escherichia coli (E. coli) to Colon Carcinogenesis // Microorganisms. ‒ 2024. ‒ Vol.12, №6.

Jans M., Kolata M., Blancke G. et al. Colibactin-driven colon cancer requires adhesin-mediated epithelial binding // Nature. ‒ 2024. ‒ Vol.635, №8038. ‒ P.472-480.

Nougayrède J.P., Homburg S., Taieb F. et al. Escherichia coli induces DNA double-strand breaks in eukaryotic cells // Science. ‒ 2006. ‒ Vol.313, №5788. ‒ P.848-851.

Gaab M.E., Lozano P.O., Ibañez D. et al. A Meta-Analysis on the Association of Colibactin-Producing pks+ Escherichia coli with the Development of Colorectal Cancer // Lab Med. ‒ 2023. ‒ Vol.54, №1. ‒ P.75-82.

Cougnoux A., Dalmasso G., Martinez R. et al. Bacterial genotoxin colibactin promotes colon tumour growth by inducing a senescence-associated secretory phenotype // Gut. ‒ 2014. ‒ Vol.63, №12. ‒ P.1932-1942.

Oliero M., Cuisiniere T., Ajayi A.S. et al. Putrescine Supplementation Limits the Expansion of pks+ Escherichia coli and Tumor Development in the Colon // Cancer Res Commun. ‒ 2024. ‒ Vol.4, №7. ‒ P.1777-1792.

Kulmambetova G., Kurentay B., Gusmaulemova A. et al. Association of Fusobacterium nucleatum infection with colorectal cancer in Kazakhstani patients // Front Oncol. ‒ 2024. ‒ Vol.14. ‒ P.1473575.

Miyasaka T., Yamada T., Uehara K. et al. Pks-positive Escherichia coli in tumor tissue and surrounding normal mucosal tissue of colorectal cancer patients // Cancer Sci. ‒ 2024. ‒ Vol.115, №4. ‒ P.1184-1195.

Oliero M., Hajjar R., Cuisiniere T. et al. Inulin impacts tumorigenesis promotion by colibactin-producing Escherichia coli in Apc(Min/+) mice // Front Microbiol. ‒ 2023. ‒ Vol.14. ‒ P.1067505.

Woon J.Y., Vidanapathirana G., Lam A.K. et al. Systematic Analysis of the Differential Effects of Red Meat on Colorectal Cancer Risks: A Meta-Analytic Approach // J Gastrointest Cancer. ‒ 2025. ‒ Vol.56, №1. ‒ P.170.

Ungvari Z., Fekete M., Varga P. et al. Association between red and processed meat consumption and colorectal cancer risk: a comprehensive meta-analysis of prospective studies // Geroscience. ‒ 2025. ‒ Vol.47, №3. ‒ P.5123-5140.

Sandhu M.S., White I.R., McPherson K. Systematic review of the prospective cohort studies on meat consumption and colorectal cancer risk: a meta-analytical approach // Cancer Epidemiol Biomarkers Prev. ‒ 2001. ‒ Vol.10, №5. ‒ P.439-446.

Arima K., Zhong R., Ugai T. et al. Western-Style Diet, pks Island-Carrying Escherichia coli, and Colorectal Cancer: Analyses From Two Large Prospective Cohort Studies // Gastroenterology. ‒ 2022. ‒ Vol.163, №4. ‒ P.862-874.