Bacterial Invasin: Structure, Function, and Implication for Targeted Oral Gene Delivery

Abstract

The mucosal surface of the gastrointestinal (GI) tract is the first line of defense against foreign pathogens and toxins ingested orally. The content of the GI tract is constantly being sampled by the immune system through specialized epithelial cells known as M-cells, which are present in the Peyer's patches of the gut, providing a thin covering over lymphoid tissue. In this way, once a harmful entity is found an immune response can be activated to eliminate the threat. Many bacterial pathogens, such as Yersinia, Listeria, Salmonella, and Shigella, have evolved ways of exploiting M-cells to gain entrance to the body. The Yersinia species is of particular interest since its extracellular protein invasin provides one of the most direct and efficient manners of host cell invasion. Invasin binds to a subset of beta1 integrin receptors located on the apical membrane of intestinal M-cells, thereby facilitating the bacteria's entry into the cells and the lymphatic system underneath. This mechanism is highly specific and effective, making the invasin protein a very attractive modality for use in the oral delivery of molecules that include therapeutic genes and gene-based vaccines. This article provides a brief overview of the molecular structure and properties of the Yersinia invasin as related to the protein's ability to facilitate binding and entry into M-cells. Also discussed are several innovative approaches that demonstrate the use of invasin as an effective targeting agent for biological and synthetic gene carrier systems, and the future prospect of developing invasin-based oral gene delivery formulations.

Freeze-Dried Targeted Mannosylated Selenium-Loaded Nanoliposomes: Development and Evaluation

“…M cells have a high transcytotic capacity, making them able to transport many materials and particulates. Therefore, they are a potential gateway for the delivery of drugs, vaccines, and other biologics (33,103,104). The coating of mannosamine on the surface of the Se-loaded nanoliposomes will serve as mucoadhesive and ligand for mannose receptor loaded on M cells.…”

Bacteria induce CTGF and CYR61 expression in epithelial cells in a lysophosphatidic acid receptor-dependent manner

“…Eukaryotic organisms have evolved several important pattern recognition mechanisms to sense bacterial products such as lipopolysaccharides for innate immune defense as shown for Toll-like receptors and Nod (Chamaillard et al, 2004;Takeda and Akira, 2005;Karin et al, 2006). In addition, virulence factors of bacteria have evolved to enable binding to distinct receptors for adhesion, invasion, or as transporters to deliver bacterial products such as toxins into host cells (Niemann et al, 2004;Palumbo and Wang, 2006) including different surface molecules such as, for example, b-integrins, cadherins, or syndecans (Isberg and Barnes, 2001;Lecuit et al, 1999;Henry-Stanley et al, 2005). Our data suggest an additional mechanism as to how host responses upon interaction with bacteria might be induced.…”

Proteinaceous determinants of surface colonization in bacteria: bacterial adhesion and biofilm formation from a protein secretion perspective

“…The intimin/invasin family regroups adhesins that mediate bacterial adhesion and/or invasion of their host cells. In Yersinia spp., invasin binds to mammalian cell receptors of the integrin family (Isberg et al, 2000; Palumbo and Wang, 2006). In enteropathogenic E. coli , intimin mediates intimate adherence between the bacteria and the host cells by interacting with Tir (translocated intimin receptor) (Frankel and Phillips, 2008).…”