Molecular Insights on Shigellosis: How the Interaction Between Invasin IpaA and Vinculin Hijacks Cellular Mechanotransduction

Abstract

With 270 million infections annually and nearly half a million death a year, shigellosis is a severe intestinal infection caused by bacteria of the Shigella family. Appearance and spread of drug-resistant strains renewed global concerns for public health and finding novel targets for treatment is fast becoming a priority. To this end, invasins are a potentially good candidate. Also called Ipa(s), which is the short for Invasion Plasmid Antigen, invasins play a key role in mediating bacterial invasion and infection of the host cell. Importantly, they have been reported to hijack inbuilt mechanical capability of the host cells such as cell adhesion and active processes mediated by the actin cytoskeleton to enable bacterial ingress into the host cells. IpaA is an invasin of particular interest as it presents three motifs that mimic vinculin binding sites and thus it allows IpaA to interact with vinculin, which is one of the most critical regulators of cellular and tissue mechanics. Using a mechanobiology point-of-view, we aim to provide an overview of Shigella´s infection mechanism, to highlight recently discovered molecular mechanisms of IpaA/vinculin interaction and to finally discuss their consequences for epithelial cell and tissue mechanical homeostasis that may result in the symptomatic outcomes seen in severe shigellosis.