The role of adhesins of Fusobacterium nucleatum in colorectal cancer - a structural perspective.

Fusobacterium nucleatum is frequently found in the colon microbiome of colorectal cancer (CRC) patients. The bacterium is not only a passive bystander of CRC, but is actively involved in disease progression through mediating tumor growth stimulation, metastasis, and immune evasion. These outcomes are achieved through the action of several adhesins that are located on the outer membrane surface of F. nucleatum, which bind to different receptors on tumor or immune cells. Adhesin-receptor interaction as the initial step of host-pathogen interaction then triggers signal transduction pathways responsible for uncontrolled cell growth or downregulation of immune cells. For a number of CRC-relevant adhesins of F. nucleatum (FadA, Fap2, CbpF), the receptors have been known already for several years, but only recently mechanistic details have been elucidated through the determination of high-resolution structures of the complexes. In the case of other adhesins (RadD, Aim1), receptors have only recently been identified, or are as of yet unknown, and the mechanistic details underlying the interaction remain enigmatic. Here, we review the relevance of particular F. nucleatum adhesins in CRC progression, with a focus on recent mechanistic insights derived from structural biology.