Team of CRIG researcher Prof. Lars Vereecke & collaborators discover how specific E. coli bacteria drive colon cancer

CRIG

Colon cancer ranks as the third most prevalent and deadliest type of cancer. Alarmingly, its incidence is rising, particularly among young people. Emerging evidence indicates that certain bacteria in the gut microbiota (the collection of primarily healthy bacteria in our intestines) can promote the development of colon cancer, through largely unknown mechanisms.

One of the suspected cancer-promoting bacteria is pks+ E. coli, which produces a genotoxin called ‘colibactin’. Colibactin is capable of binding and damaging human DNA, causing mutations that can increase the risk of cancer. These bacteria and the mutations they induce are remarkably overabundant in patients with colon cancer.

Until now, it was unclear how pks+ E. coli could reach and damage the gut wall to promote cancer development. The experiments by the teams of Prof. Lars Vereecke (CRIG, VIB-UGent) and Prof. Han Remaut (VIB-VUB) revealed that these bacteria switch between a free-swimming state and a mode where they attach to the gut tissue lining (the intestinal epithelium). This attachment is made possible by specific bacterial pili, long thin protein fibers on the bacterial surface that end in adhesins that can bind receptors on the cells of the intestinal epithelium.  

We found that this pilus binding significantly increases the number, size, and aggressiveness of colon tumors.
- Maude Jans (CRIG, VIB-UGent, first author of the study)
 

Our experiments reveal that the binding of pks+ E. coli to the intestinal epithelium can be regarded as a critical step in the development of colon cancer. We found that by interfering with these bacterial attachment mechanisms, tumor development could be strongly attenuated. 
- Prof. Lars Vereecke (CRIG, VIB-UGent), senior author of the study

The researchers were able to identify the specific bacterial adhesins that mediate binding to colon cells and hypothesized that the binding by these adhesins allows bacteria to produce the genotoxin colibactin nearby epithelial cells, which leads to DNA damage and cancer development. Sure enough, the team demonstrated that the removal of the adhesins takes away the ability of the bacteria to deliver colibactin and cause DNA damage. 

Based on these discoveries, a therapeutic approach was tested to prevent bacterial attachment using molecules that block the binding of these essential bacterial adhesins. 

Remarkably, we could drastically suppress DNA damage and tumor development in preclinical models. This therapy approach is very promising since it successfully targets harmful E. coli strains, without affecting beneficial gut microbes, unlike antibiotics.
-Maude Jans (CRIG, VIB-UGent, first author of the study)

The results have recently been published in the top scientific journal 'Nature', underscoring the importance of these findings. 

To help disseminating these research results to a broad audience, the teams also made an animation video about their study that was financially supported by CRIG: