Breakthrough in Gut Bacterial Adhesion: New Targets for Colorectal Cancer Treatment

Recent research has uncovered critical insights into how Fusobacterium nucleatum (F. nucleatum), an anaerobic bacterium commonly found in the gut microbiota of colorectal cancer (CRC) patients, promotes tumor development. The study, led by Professor George F. Gao from the Chinese Academy of Sciences, focused on the bacterium's ability to adhere to cancer cells, a key step in infection and disease progression. F. nucleatum uses its adhesin protein, CbpF, to specifically bind to human receptors CEACAM1 and CEACAM5, which are frequently overexpressed on various cancer cells.

Understanding this adhesion mechanism is vital because CEACAM1, when engaged, also acts as an immune inhibitory receptor, dampening immune responses and facilitating tumor growth. To unravel how CbpF interacts with these receptors at the molecular level, researchers employed cryo-electron microscopy to resolve high-resolution structures of the complex. They discovered that CbpF forms a trimer, with each monomer binding to a CEACAM molecule, creating a symmetric 3:3 complex. Interestingly, they also observed complexes where two CbpF trimers bind to a single receptor dimer.

Based on these findings, the team proposed a 'Velcro model' for bacterial adhesion. This model suggests that the flexible CbpF acts as a 'loop,' with multiple binding sites that interact with the host's receptors like 'hooks,' allowing bacteria to dynamically regulate adhesion strength. This adaptable mechanism enables tight attachment or detachment under mechanical stress, aiding bacterial survival and potentially promoting tumor progression.

These insights open new avenues for therapeutic intervention, aiming to disrupt bacterial adhesion and hinder colorectal cancer development. This innovative research was published in the Proceedings of the National Academy of Sciences, highlighting the importance of molecular understanding in tackling bacterial contributions to cancer.