Shigella is a group of bacteria responsible for causing shigellosis, an acute intestinal infection characterized by inflammatory diarrhea, sometimes called bacillary dysentery. The infection begins when the bacteria are ingested, often through contaminated food or water, and survive the acidic environment of the stomach to reach the intestinal tract. The bacteria are highly infectious, with as few as 10 to 100 organisms being enough to initiate an infection.
Anatomical Site of Infection
The primary anatomical location where Shigella establishes its infection is the large intestine, particularly the colon and the rectum. After passing through the upper digestive tract, the bacteria multiply in the small intestine before moving into the colon, where the pathogenic events mainly occur. This preference for the large intestine contrasts with many other diarrheal pathogens, which primarily target the small intestine to cause watery diarrhea by releasing toxins that interfere with water and electrolyte absorption.
In the colon, Shigella must penetrate the epithelial layer, the protective cellular barrier lining the intestine, to cause disease. The resulting inflammatory colitis leads to the characteristic symptoms of dysentery, including bloody and mucus-tinged stools. The bacteria generally remain within the mucosa and rarely penetrate beyond this layer, which helps explain why bloodstream infections (bacteremia) are uncommon in shigellosis.
The Initial Target Cell
The initial site of attachment and entry into the intestinal lining is a specialized cell type known as the Microfold (M) cell. These cells are found interspersed within the epithelium covering the Peyer’s patches, which are organized lymphoid tissues located beneath the intestinal lining. M cells are designed to sample antigens from the gut lumen and transport them across the epithelial barrier to the immune cells waiting below.
After being taken up by the M cell, the bacteria are transcytosed, or transported across the cell, without causing significant immediate damage. Once Shigella breaches the epithelial barrier, it is released into the subepithelial space, where it encounters resident immune cells, such as macrophages, and the basolateral side of the abundant epithelial cells.
Cellular Machinery for Entry
To force its way into host cells, whether the initial M cell or the epithelial cells from the basolateral side, Shigella utilizes the Type III Secretion System (T3SS). The T3SS is a syringe-like nanomachine composed of approximately 20 different proteins that span the bacterial membranes, forming a hollow needle structure. This apparatus allows the bacteria to directly inject a suite of effector proteins from its own cytoplasm into the host cell’s cytoplasm.
These injected effector proteins, such as IpaA, IpaC, IpgB1, and IpgB2, manipulate the host cell’s internal machinery. Their primary target is the host cell’s actin cytoskeleton, a network of protein filaments that controls cell shape and movement. The effectors cause rapid and massive polymerization of actin beneath the host cell membrane at the site of bacterial contact.
This intense actin remodeling creates large, temporary surface protrusions known as “membrane ruffles.” The formation of these ruffles effectively encircles and engulfs the Shigella bacterium, pulling it into the host cell in a process that resembles host-cell phagocytosis, but is entirely orchestrated by the pathogen.