The anticancer activity demonstrated by genetically attenuated invasive Shigella flexneri contradicts the long-held understanding of bacterial infection-mediated anticancer activity (BIMAc), as a ‘by-stander effect’ caused by an immune response against any invading pathogen as a reason for tumour regression. Similarly, the selective tumouricidal effect by Salmonella A1 auxotrophic mutant in nude mice is another observation where the current theory fails. Considering these flaws, we set to re-examine the mechanisms behind BIMAc independent of immune response, on the basis of molecular understanding about the initial colonisation of gut epithelium by S. flexneri and its production of cell-cycle-inhibiting proteins called cyclomodulins. During infection, S. flexneri injects OspE effector protein into the gut epithelium. The resulting interaction of OspE with ILK prevents epithelial cell exfoliation and facilitates the pathogen’s colonisation of the gut. This interaction is also shown to enhance membrane retention of ILK in these infected cells. Correspondingly, another study reports the indispensable role of ILK in survival of cancer cells with supernumerary centrosomes by localising it to the centrosomes and clustering them into a bipolar spindle. Knockdown of ILK in these cells leads to apoptosis due to multipolar mitosis. From these cumulative facts we hypothesised that enhanced membrane retention of ILK in Shigella-infected cancer cells prevents localisation of ILK to centrosomes and provokes multipolar mitosis and therefore cell death in cancer subpopulations with supernumerary centrosomes. This interaction may also be metastasis suppressive, because of its inhibitory effect on the focal adhesion turnover of gut epithelium, which is quintessential for any form of cell migration. Apart from these, Shigella also encodes potent cell-cycle-inhibiting effector molecules such as cyclomodulins. The additive action of these cyclomodulins along with the OspE–ILK interaction may be considered as the reason behind the anticancer activity mediated by Shigella infection.

Any alteration in gut microbiota may result in the colonization of certain pathobionts, leading to the development of colon diseases. Some strains of Escherichia coli are pathobionts that can contribute to the initiation or progression of colon diseases through the induction of pro-inflammatory pathways or the production of genotoxins.

The present study was performed to investigate the association between certain E. coli pathobionts (cyclomodulin-positive and afa -C+ diffusely adherent E. coli ) and their characteristics with colon diseases.

Stool specimens were collected from patients referred to colonoscopy centers at two university-affiliated hospitals (Yazd and Kerman, Iran). A total of 67 patients voluntarily joined the study as the target group (21 cases of colorectal cancer and 46 cases of inflammatory bowel disease), along with 67 healthy individuals. Stool samples were screened for E. coli isolates using culture techniques. Cyclomodulin-encoding genes ( clbN , cnf , cdt , and cif ), as well as afa -C, were detected by PCR assay. Phylogrouping, virulence gene screening, antibiotic susceptibility evaluation, and biofilm formation assessment were also performed.

In comparison with the control group, afa -C+ DAEC was significantly associated with CRC (n = 8, 38.1%, P = 0.001) and IBD (n = 8, 17.4%, P = 0.026). The presence of clb N (n = 4, 19%) and cnf (n = 4, 19%, P = 0.053) was relatively associated with CRC. Most of the isolates from the patient group (n = 16, 23.9%) belonged to phylogroup B2. Iron uptake-related genes were also significantly associated with isolates from patients. No significant association was found between antibiotic resistance and biofilm formation in any of the studied groups.

This study provides preliminary data about the involvement of certain important E. coli pathobionts in colon diseases. As afa -C+ DAEC was associated with the colon diseases studied, it appears that it may be proposed as a putative marker for screening procedures. However, a definitive conclusion requires more comprehensive investigations.