Shigella dysenteriae

Scientific classification
Kingdom:	Eubacteria;
Phylum:	Proteobacteria;
Class:	Gamma Proteobacteria;
Order:	Enterobacteriales;
Family:	Enterobacteriaceae;
Genus:	Shigella;
Species:	dysenteriae;
Binomial name
	Shigella dysenteriae;

Main Article

Discussion

Description and significance

Describe the appearance, habitat, etc. of the organism, and why it is important enough to have its genome sequenced. Describe how and where it was isolated. Include a picture or two (with sources) if you can find them.

[[1]]

Shigella was discovered over 100 hundred years ago by the Japanese biologist Shiga, which the genus was named after. ^[1] Shigella dysenteriae is gram-negative. Shigella dysenteriae are rod (bacillus) shaped, non-motile, non-spore-forming, facultative anaerobic bacteria. The bacteria is able to survive contaminated environments as well as the acidity of the human gastro-intestinal tract. The accumulation of bacterial Shigella dysenteriae is known to cause a condition known as shigellosis.

Genome structure

Describe the size and content of the genome. How many chromosomes? Circular or linear? Other interesting features? What is known about its sequence? Does it have any plasmids? Are they important to the organism's lifestyle?

Shigella dysenteriae has the smallest genome out of the genus Shigella, which contains three other species. It's genome consists of a single circular chromosome and 4,369,232 base pairs.^[2] It carries an invasion-associated plasmid which contains genes that code for the invasion of the epithelial cells and the production of Shiga toxin. ^[3] The Shiga toxin is a potent A-B type toxin with 1-A and 5-B subunits. B subunits bind to the cell and inject the A-subunit. By cleaving a specific adenine residue from the 28S ribosomal RNA in the 60S ribosome, the toxin inhibits protein synthesis, causing cell death. ^[4]

Cell structure and metabolism

Describe any interesting features and/or cell structures; how it gains energy; what important molecules it produces

Shigella dysenteriae ferments glucose via mixed acid fermentation, however it does not produce any gas. It does not produce H₂S, phenylalaninedeaminase or urease and does not use citrate as a sole carbon source. They ferment only a few cabohydrates.^[5]

Shiga Toxin

Shigella dysenteriae, produces Shiga toxin. Shiga toxin has a cytotoxic effect on intestinal epithelial cells.^[6] The molecular weight of the toxin is 68,000 da. The alpha units of the toxin are responsible for toxicity and the beta units are responsible to for binding to the host cell.^[7]

The toxin acts on the lining of the blood vessels, the vascular endothelium. The B subunits of the toxin bind to a component of the cell membrane known as Gb3 and the complex enters the cell. When the protein is inside the cell, the A subunit interacts with the ribosomes to inactivate them. The A subunit of Shiga toxin is an N-glycosidase that modifies the RNA component of the ribosome to inactivate it and so bring a halt to protein synthesis leading to the death of the cell. The vascular endothelium has to continually renew itself, so this killing of cells leads to a breakdown of the lining and to hemorrhage. The first response is commonly a bloody diarrhea. This is because Shiga toxin is usually taken in with contaminated food or water.^[8]

The toxin is effective against small blood vessels, such as found in the digestive tract, the kidney, and lungs, but not against large vessels such as the arteries or major veins. A specific target for the toxin appears to the vascular endothelium of the glomerulus. This is the filtering structure that is a key to the function of the kidney. Destroying these structures leads to kidney failure and the development of the often deadly and frequently debilitating hemolytic uremic syndrome. Food poisoning with Shiga toxin often also has effects on the lungs and the nervous system.^[9]

Ecology

Describe any interactions with other organisms (included eukaryotes), contributions to the environment, effect on environment, etc.

Shigella dysenteriae can survive in faecally contaminated materials which can include water, foods, and other materials.^[10] It can be transmitted by person to person contact. It is generally transmitted with the ingestion of water and food contaminated with the bacteria. It can cause foodborne or waterborne epidemics. Shigella infections may be acquired from eating food that has become contaminated by infected food handlers. Vegetables can become contaminated if they are harvested from a field with contaminated sewage or wherein infected field workers defecate. Shigella can also be transmitted by flies. Flies can breed in infected feces and then contaminate food. Shigella infections can be acquired by drinking or swimming in contaminated water. Water may become contaminated if sewage runs into it, or even if someone with shigellosis swims or bathes or, worse, defecates, in it.^[11] Epidemics are more likely in poorer countries without adequate sanitation and water treatment systems.

Pathology

How does this organism cause disease? Human, animal, plant hosts? Virulence factors, as well as patient symptoms.

Shigella dysenteriae causes shigellosis (bacillary dysentery) in humans. It's also known to cause dysentery in other primates, but not in other animals. The infection can be caused by as little as 10 bacterial cells, whereas as other bacteria requires millions on cells for infection.^[12] The infection begins with the bacteria entering the gastro-intestinal tract attaching itself to the intestinal wall. Following host epithelial cell invasion and penetration of the colonic mucosa, Shigella infection is characterized by degeneration of the epithelium and inflammation of the lamina propria. This results in desquamation and ulceration of the mucosa, and subsequent leakage of blood, inflammatory elements and mucus into the intestinal lumen. Patients suffering from Shigella infection will therefore pass frequent, scanty, dysenteric stool mixed with blood and mucus, since, under these conditions, the absorption of water by the colon is inhibited, leading to dehydration^[13]

Common symptoms of bacillary dysentery include acute bloody diarrhea, abdominal pains and cramps, fever, vomiting, dehydration, and tenesmus.^[14] The significant complication is hemolytic uremic syndrome, which develops in 5 to 10 percent of patients. Mortality from hemolytic uremic syndrome approaches 5 percent, but up to 30 percent of patients who survive have chronic renal disease.^[15]

Shigellosis usually resolves on its own in several days, but in smaller children and people with weak immune systems, the infection can be more severe, resulting in hospitalization or death. Once a person has become infected, they are not likely to get infected with the particular strain again, due to the bodies ability to produce antibodies. However, they can be reinfected by other strains of Shigella dysenteriae.^[16] Treatment, used generally in more severe cases, includes the application of antibiotics. The antibiotics will kill the bacteria inside the gastrointerstinal tract, shortening its lifespan and therefore shortening the course of the infection.^[17] Ciprofloxacin and ampicillin are frequently used to treat the infection, however, Shigella dysenteriae is becoming more susceptible to antibiotic resistance than other species in the genus Shigella.^[18]

Application to Biotechnology

Does this organism produce any useful compounds or enzymes? What are they and how are they used?

Current Research

Enter summaries of the most recent research here--at least three required

Recent studies have shown that Shigella dysenteriae, as well as other species within the genus, are becoming significantly more resistance to antibiotics in the United States. This resistance has made cases of infection by Shigella dysenteriae more difficult to treat, especially in children. Shigella are becoming more resistant to treatments which use ampicillin and trimethoprim-sulfamethoxazole (TMP-SMX). Shigella isolates were surveyed over a period of four years, and the there was a common trend in increasing rates of resistance to these animicrobial agents. Shigella dysenteriae isolates are also developing a resistance to nalidixic acid. It was also found that these resistances were not limited to the United states. Shigella dysenteriae isolates are becoming more resistant to antimicrobial agents in other parts of the world as well.^[19]

It has been found that Shigella dysenteriae's virulence is regulated by RyhB suppression. The virulence genes that are being repressed by RyhB includes genes which code for the secretion apparatus, its effectors and its chaperones. It was found that the virulence suppression was occurs by the RyhB dependent repression of the transcriptional activator VirB which lead a reduction in expression of genes within the VirB region. Several tests were conducted such as microarray analysis, secreted protein analysis and Polymerase Chain Reaction. It was concluded that RyhB represses the expression of several genes within VirB region, which in turn, suppresses plaque formation by inhibiting the ability of Shigella dysenteriae to invade eukaryotic cells. There is a direct relationship between plaque formation and RyhB expression. It was then further determined that since RyhB is iron-responsive, iron, therefore contributes to the regulation of virulence within Shigella dysenteriae.^[20]

There has been one case of Shigellosis discovered in which the patient suffered from septic shock and convulsions, which is an unusual side effect of the infection. The patient had the usual symptoms of bloody diarhhea, tenesmus and fever. The patient also suffered from abnormal body movement and did not respond to the initial treatments with trimethoprim-sulphamethoxazole, which suggests that the particular strain of the infection was resistant to the antibiotic. Various tests, such as blood films, stool microscopy, stool culture and cerebrospinal fluid cultures, were conducted to determine the cause of this case of Shigellosis, but all came up negative. Finally, a tests was done on the blood culture and after a few days colony growth was observed and Shigella dysenteriae was isolated. Sensitivity test were then conducted on the bacteria. It was determined that the bacteria was resistant to chloramphenicol, TMP-SMX, ampicillin, and tetracycline, but sensitive to ciprofloxacin and gentamycin. The patient was given medication for the septic shock, which subsided soon afterward. However, the patient died soon after. It was thought that the septic shock was a result of the build up of Shiga toxin produced by the bacteria. It was concluded that when not appropriately and promptly treated, these infections can lead to more serious and lethal side effects.^[21]