Modern Aspects on <i>Shigella</i> Pathogenecity and Vaccine Development - A Review

Abstract

Shigella species are intracytosolic Gram-negative invasive enteropathogenic bacteria, causing the rupture, invasion and inflammatory destruction of the human colonic epithelium. They utilize the host cytoskeletal components to form propulsive actin tails. The so-called invasive phenotype of Shigella is linked to expression of a type III secretory system (TTSS) injecting effector proteins into the epithelial cell membrane and cytoplasm, thereby inducing local but massive changes in the cell cytoskeleton that lead to bacterial internalization into non-phagocytic intestinal epithelial cells. The molecular and cellular bases of this invasive phenotype essentially encompass crossing of the epithelial lining, apoptotic killing of macrophages, entry into epithelial cells, and escape into the cytoplasm, followed by cell-to-cell spread. Intracellular colonization is likely to protect the microorganisms from killing by humoral and cellular effectors of the innate immune response. Concurrently, the capacity of Shigella to reprogram invaded epithelial cells to produce proinflammatory mediators plays a major role in the strong inflammatory profile of the disease. This profile is likely to impact on the nature and quality of the adaptive response, which is dominated by humoral protection at the mucosal level. In recent years, a large amount of information has been generated regarding the host, pathogen and environmental factors that impact the pathogenesis of shigellosis at the cellular and molecular level. This review summarizes what is currently known about Shigella, detailing those factors that contribute to pathogenesis and examining the current progress in the development of a vaccine.