Shigella Infection (Shigellosis) Antibodies, Proteins & ELISA Kits

Shigellosis is a disease caused by the gram-negative, facultative anaerobic Shigella species of bacteria. Shigella infections can be caused by contaminated food, person to person contact and from poor sanitation conditions. S.dysenteriae, S.flexneri, S.boydii and S.sonnei are the main pathogens involved in shigellosis.

S.sonnei is mainly found in industrialized countries, whereas, S.dysenteriae, S. boydii, S.flexneri are predominantly found in developing regions with tropical climates such as Sub-Saharan Africa and South Asia. It is estimated that Shigella causes 80-165 million cases of disease which results in 600,000 deaths each year. The symptoms observed in shigellosis infections are fever, vomiting, abdominal pain, tenesmus, bloody diarrhea and severe cases can lead to death. There is a current need for more research into Shigella pathogenesis in shigellosis infections in order to develop a vaccine to prevent transmission of the disease.

S.dysenteriae serotype 1 produces shiga toxin and some strains of Escherichia coli produce shiga-like toxin. There is an almost identical similarity between amino acid sequences of shiga toxin and shiga-like toxin and both can be used as research tools for vaccine studies.

Shiga and shiga-like toxin are composed of A and B subunits. The B subunit helps to bind the toxin to the host cell membrane where the toxin is then engulfed by the cell. Due to the increase in acidity inside the cell the disulfide bond between the A and B subunits breaks. The A subunit can then diffuse into the cytoplasm and target the ribosome to stop the host cells synthesizing proteins, ultimately leading to their destruction.

Experiments were previously performed with rhesus monkeys which were infected with S dysenteriae 1 and Shiga toxin-negative mutants. The results were that the cytotoxin is responsible for causing destruction of capillaries because they destroy endothelial cells leading to gaps in capillary walls and they also cause faecal hemorrhage which leads to diarrhea.

Toll-like receptor 4 (TLR4) is an immune host receptor which is responsible for binding to LPS (Lipopolysaccharide) on Shigella species. As well as this, infection with S.flexneri and S.sonnei have been shown to activate the NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome when the nucleotide-binding and oligomerization domain (NOD)-like receptor NLRP3 recognizes pathogen-associated molecular patterns (PAMPs) of Shigella species. NLRC4 inflammasomes are also activated when NLR family of apoptosis inhibitory proteins (NAIP) recognizes Shigella species.

Macrophages try to phagocytose Shigella species and in turn they undergo apoptosis releasing inflammatory cytokines like interleukin-1beta (IL-1beta). The release of IL-1beta recruits other immune cells to the site of infection which causes inflammation and death of epithelial cells, ultimately damaging the colonic mucosa. Polymorphonuclear leukocytes (PMN) are recruited to the site of infection and they cause disruption between the junctions of neighboring epithelial cells. This allows Shigella species to infect colonic enterocytes.

The recruitment of immune cells causes the release of a wide range of cytokines such as IL-6, IL-8, IL-17A, IL-18, IL-22, IL-1beta, interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), TNF-beta, IL-10 and transforming growth factor-beta (TGF-beta). As well as this, there have been reports of Shigella downregulating beta-defensin and CCL20 chemokines which causes a defective recruitment of dendritic cells to the site of infection.

Immunometabolism is an important area of science which encompasses regions of metabolism and immunology. Many of the functional capacities of immune cells are dependent on the metabolic state of the cell and its capability to mount an immune response.

It was shown that infection with Shigella species causes an increase in the permeability of infected human monocyte-derived macrophage’s (HMDMs) cell membrane. It was also observed that there was a 50% decrease in adenosine triphosphate (ATP) production in Shigella infected HMDMs and that the mitochondrial membrane potential was lost. The mitochondria is the location where oxidative phosphorylation (OxPhos) metabolism occurs meaning that Shigella infections are causing a decrease in energy production in HMDMs and in turn a defective immune response. It was also shown that both reactive oxygen species (ROS) and nitric oxide (NO) species are produced during Shigella infections which can lead to oxidative damage to mitochondrial components.

The main host for Shigella species are humans but there have been reports of infections in rabbits, piglets, chickens, calves and other primates such as monkeys. Animal models are useful research tools which are often used in early stages of therapeutic product development and pathogenesis studies. Non Human Primate (NHP) models such as the macaque monkey model are used for analyzing Shigella pathogenesis and it was observed that acute colitis observed in human infections is similar in monkey models of disease. Assay Genie provides a wide range of animal model ELISA kits for research purposes which could aid in understanding the mechanism of shigellosis disease.