Shigella species are a group of human-adapted bacteria that target the large intestine and cause shigellosis, a diarrheal disease that can range from mild to life-threatening. These bacteria are highly efficient invaders of the gut lining. After entering the colon, they slip beneath the surface layer of intestinal epithelial cells and invade from the basolateral side, which is the underside of the cell that normally does not encounter microbes. To do this, Shigella uses a type III secretion system, a needle-like structure the bacterium uses to inject proteins directly into human cells. These proteins reorganize the cell’s internal scaffolding, allowing Shigella to enter, move within the cell, and spread to neighboring cells.
Once inside the gut lining, Shigella multiplies and moves from cell to cell, creating pockets of infection and significant tissue damage. Some species, such as Shigella dysenteriae, produce Shiga toxin, a protein that can further injure the intestinal lining and worsen disease severity. Other proteins, such as SepA and SigA, weaken the gut’s protective barrier by degrading structural components and increasing permeability. This breakdown of the epithelial barrier allows fluid to leak into the gut, contributing to watery diarrhea early in infection.
The host immune system responds vigorously to Shigella. Even very small numbers of these bacteria can trigger intense inflammation. Neutrophils rapidly flood into the gut tissue, helping clear the infection but also damaging the intestinal lining. As the infection progresses, inflammation and tissue breakdown can cause dysentery, which is diarrhea containing blood and mucus.
Shigella also manipulates the gut environment to its advantage. It reduces local oxygen levels, which helps the bacteria survive and spread in tissues that are normally only partially oxygenated. It can also take advantage of natural gut peptides such as human alpha-defensin 5 by binding to it in ways that increase bacterial adhesion and invasion.
Modern experimental systems like organoids and organ-on-chip platforms have provided deeper insight into these processes. These models show how gut architecture, fluid flow, and mechanical forces influence Shigella’s ability to colonize the epithelium and highlight the broad set of bacterial genes required for successful invasion and replication.
Infection is highly contagious. As few as 10 to 100 organisms can cause disease, explaining why outbreaks often occur in settings where close contact is common. While most cases are limited to the gut, some infections contribute to complications such as growth impairment and metabolic changes in vulnerable populations.