Shigella Species

Abstract

Shigella is highly infective and causes disease worldwide. In particular, it causes frequent outbreaks in economically poor countries, parts of Asia, sub-Saharan Africa, and South America and is mostly associated with unhygienic and poor sanitary living conditions. S. dysenteriae type 1 causes epidemic outbreak and S. flexneri and S. sonnei cause endemic outbreaks. Shigella expresses multiple virulence factors encoded in a large plasmid. The major virulence genes are encoded in a 30 kb pathogenicity island as well as are scattered on a large plasmid. The virulence proteins are required for bacterial invasion, intracellular growth, cell-to-cell spread, killing of host cells, and evasion of the host innate defense system. The virulence proteins are delivered to the host cell by type III secretion system (T3SS). After being ingested with contaminated drink or food, bacteria colonize the colon and rectal mucus membrane. The infection dose is very low, 10–100 cells, because, in part, of their ability to survive gastric acid (pH 2.5). Bacteria cross the epithelial barrier by passing through naturally phagocytic M cells. After arrival in the subcellular location, they are engulfed by macrophages, neutrophils, and dendritic cells. Bacteria kill these cells by apoptosis and invade epithelial cells in the basolateral side by inducing membrane ruffling and macropinocytosis, a mechanism termed as “trigger mechanism.” This process is aided by bacterial ability to deliver many virulence proteins called effectors by T3SS. Bacteria are then released from phagosome with the aid of IpaB, avoid autophagy using IcsB, move inside the cell by inducing actin polymerization with the help of IcsA, and infect the neighboring cell. Infection results in the release of high levels of proinflammatory cytokines (IL-1β, IL-8, IL-18) that recruit neutrophils and NK cells. Bacteria-induced epithelial cell damage and the activation of neutrophils result in massive inflammation characterized by ulceration and hemorrhage, and patients show signs of mucopurulent bloody stool, abdominal cramp, and tenesmus. Children under the age of 5 are most susceptible, and the infection could be fatal in malnourished children.