Can bacteria F. nucleatum be actively involved in colon cancer progression via a radical mediated mechanism?

Outer membrane proteins of Fusobacterium nucleatum, a cancer­leading bacteria, are considered as the factors responsible for its pathogenicity. Among them, homotrimeric autotransporter protein YadA (Yersinia adhesin A) is an important virulence factor also found in the outer membrane of pathogenic Yersinia species. In this paper, the structure and stability of certain Cu(II) complexes with YadA fragments were investigated using both, experimental and theoretical methods. Potentiometry, UV-Vis, CD, EPR, and calculations at the density functional theory (DFT) level were applied to determine the metal ion coordination sphere. Moreover, the complexes ability to DNA cleavage and reactive oxygen species (ROS) production was studied. We have shown that copper(II) complexes can cleave DNA by 1O2, O2•- and •OH, which are formed in the studied systems. However, the results of electrophoretic experiments revealed that complexes cleave DNA less effectively than free copper(II) ions. Therefore, the presence of studied peptides may prevent DNA from a Cu(II)-induced damage to some extent.

Might Cu(II) binding, DNA cleavage and radical production by YadA fragments be involved in the promotion of F. nucleatum related cancers?

In many cases, human microbiota are associated with cancer progression. It was concluded that Fusobacterium nucleatum increases neoplastic changes. This bacterium is naturally present in human dental plaque. However, if it is present in the colon, it becomes a precursor of cancer. Antibiotic treatment of mice infected with F. nucleatum slowed tumor growth, which agrees with the fundamental role of bacteria in tumorigenesis. Remarkably, recent studies indicate that transition metal complexes with fragments of outer membrane proteins are able to promote reactive oxygen species (ROS) formation and are responsible for oxidative stress, which consequently leads to cell damage. Therefore, in this paper, the formation of copper(II) complexes with fragments of adhesin YadA from F. nucleatum is characterized. Moreover, the ability of the complexes to produce ROS has been shown. Importantly, free ligands are efficient DNA-cleaving agents.