Bacterial nucleomodulins and cancer: An unresolved enigma

Abstract

Recent studies in microbial pathogenesis have identified several bacterial proteins with the potential to influence host cell nuclei. This field of research is in its infancy, however it is rapidly growing. In particular, the role of bacterial nucleomodulins in animal oncogenesis is an area that requires attention. Earlier research has suggested the role of nucleomodulins in plant tumor development and these findings may provide us with a better understanding of the role of these proteins in human cancer development. This proposition is further supported by previous identification of nucleomodulins present in bacteria that have been associated with cancer development, but their role in human cancer is unclear. In this article, we provide an update on the status of these nucleomodulins and their role in cancer etiology. We collected information about known bacterial nucleomodulins and tried to relate their mechanistic implication with already known plant tumor development model. The present research indicates that bacterial nucleomodulins may be an important target in cancer etiology and knowledge of their role in human oncogenesis may help us to create suitable alternative cancer management strategies.

Keywords: Host-pathogen interaction; Infection; Oncogenesis; Pathogens; Protein targeting.

Graphical abstract

Fig. 1

Possible strategies for bacterial nucleomodulin mediated alteration of cellular functions that may contribute to cancer development. The orange circles represent possible molecular targets of bacterial nucleomodulins.

Fig. 2

Schematic representation of the tumor development process in plants by Agrobacterium-mediated transformation. The process involves several bacterial nucleomodulins and the transfer of nucleomodulins producing machinery in the host cell nucleus as T-DNA. The bacterial VirA senses host plants and activates the VirG protein through phosphorylation, which, in turn, activates the expression of proteins from the vir region of T-DNA. Vir D1 and VirD2 proteins act as endonucleases to release ss T-DNA from Ti-plasmid by strand replacement.VirD4, along with other 11 VirB proteins, make T4SS to transfer bacterial molecules into the host cell. VirD2 binds with T-DNA to make an immature T-complex. Other molecules including VirD5, VirE2, VirE3, and VirF are also translocated into the host cell. The VirD2-T DNA complex binds with VirE2 in the host cell to make a mature T-complex. VirD2 and VirE2 contain nuclear localization signals and transport the mature T-complex into the host cell nucleus . VirD5, VirE3, and VirF are also translocated into the host cell nucleus. VirF is supposed to help in the uncoating of the mature T-complex and facilitate its integration into host cell genetic material . VirD5 localizes to the host's centrosome/kinetochore while VirE3 act as a transcriptional activator for the induction of the expression of certain genes . The whole machinery involves several nucleomodulins that lead to increased growth and production of tumor in the host cell. Other membranes between bacterial and plant cells are not shown for the ease of simplicity in the figure.

Fig. 3

Nucleomodulins from cancer-associated bacteria and their subsequent effects on host cell nuclei. These are just a few out of a larger, more complete list which is beyond the coverage of this figure.The nucleomodulins targeting different nuclear aspects are shown in different colors. The nucleomodulins can have variety of other consequences on the host cells, but only primary effects mentioned in the literature are shown here.