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.