Shigella dysenteriae- Pathogenicity and Clinical Manifestation

Shigella dysenteriae is a type of bacteria that causes a severe form of intestinal infection called shigellosis or bacillary dysentery. Shigellosis is characterized by bloody diarrhea, fever, abdominal cramps, and tenesmus (straining to defecate). Shigellosis can lead to serious complications such as dehydration, sepsis, and hemolytic uremic syndrome (HUS), which is a life-threatening condition that affects the kidneys and blood cells.

Shigella dysenteriae belongs to the genus Shigella, which consists of four species: S. sonnei, S. flexneri, S. boydii, and S. dysenteriae. These bacteria are Gram-negative, non-spore-forming, facultatively anaerobic, and nonmotile rods. They are closely related to Escherichia coli (E. coli) but differ in their ability to invade and replicate in the cells lining the colon.

Shigella dysenteriae is the most virulent species of Shigella and can cause outbreaks of epidemic dysentery in developing countries with poor sanitation and hygiene. It is also the only species that produces an exotoxin called Shiga toxin, which is responsible for the damage to the intestinal epithelium and the renal endothelium. Shiga toxin can also be produced by some strains of E. coli, such as E. coli O157:H7.

Shigella dysenteriae is transmitted by the fecal-oral route, meaning that it can spread through contaminated food, water, surfaces, or direct contact with infected people or animals. It can also be transmitted through sexual contact with someone who has a Shigella infection or who has recently recovered from one. Shigella dysenteriae is highly contagious; it takes only a small number of bacteria (10 to 200) to cause infection.

The incubation period of Shigella dysenteriae ranges from 1 to 3 days after exposure. The duration of the illness varies depending on the severity of the infection and the treatment received, but it usually lasts for 7 days. In some cases, people may develop chronic bowel problems or become asymptomatic carriers of the bacteria after recovery.

Shigella dysenteriae infection can be diagnosed by isolating and identifying the bacteria from stool samples using culture methods or molecular techniques. Antibiotic treatment is recommended for patients with severe shigellosis or those who are at risk of complications or transmission. However, antibiotic resistance is a growing problem among Shigella species, especially S. dysenteriae type 1, which can be resistant to multiple classes of antibiotics. Therefore, prevention measures such as improving sanitation and hygiene, providing safe water and food, and promoting handwashing are essential to control the spread of Shigella dysenteriae infection.

Shigella dysenteriae is a gram-negative, rod-shaped bacterium that causes shigellosis, a severe form of bacillary dysentery. Shigella dysenteriae belongs to the family Enterobacteriaceae and has four serogroups: A, B, C, and D. Serogroup A contains the most virulent strain, S. dysenteriae type 1, which is responsible for most outbreaks of shigellosis worldwide.

Shigella dysenteriae causes disease by invading and replicating the cells lining the colon. It has several mechanisms to achieve this:

• Adherence: Shigella dysenteriae uses structural gene proteins called invasion plasmid antigens (Ipa) to attach to the surface of epithelial cells and M cells (specialized cells that transport antigens across the intestinal mucosa). These proteins are encoded by a large virulence plasmid (IPV) that is essential for the pathogenicity of Shigella. The Ipa proteins also trigger the secretion of inflammatory cytokines by the host cells, which attract immune cells to the site of infection.

• Invasion: Shigella dysenteriae uses a type III secretion system (T3SS) to inject four Ipa proteins (IpaA, IpaB, IpaC, IpaD) into the cytoplasm of the target cells. These proteins induce membrane ruffling and actin polymerization on the cell surface, leading to the formation of an endocytic vacuole that engulfs the bacteria. Once inside the vacuole, Shigella dysenteriae escapes by lysing the vacuolar membrane with another protein called IcsA (intracellular spread antigen).

• Replication: Shigella dysenteriae replicates in the cytoplasm of the host cells by using their nutrients and energy. It also interferes with the host cell cycle and apoptosis (programmed cell death) by modulating various signaling pathways. Shigella dysenteriae can also evade the host immune system by hiding inside the host cells and avoiding exposure to antibodies and complement.

• Spread: Shigella dysenteriae spreads from cell to cell by using actin-based motility. It uses IcsA to recruit actin filaments at one pole of the bacterium and form a comet tail that propels it through the cytoplasm. It then reaches the plasma membrane of the infected cell and forms protrusions that are engulfed by adjacent cells. This process allows Shigella dysenteriae to disseminate within the colonic epithelium without being exposed to the extracellular environment.

In addition to these mechanisms, Shigella dysenteriae produces an exotoxin called Shiga toxin (Stx), which is responsible for some of the severe complications of shigellosis. Stx is composed of one A subunit and five B subunits. The B subunits bind to a specific glycolipid receptor called globotriaosylceramide (Gb3) on the surface of host cells. The A subunit then enters the cell and cleaves a specific adenine residue in the 28S rRNA of the 60S ribosomal subunit, thereby inhibiting protein synthesis and causing cell death. Stx mainly affects the intestinal epithelium and causes ulceration and bleeding in the colon. However, in some cases, Stx can enter the bloodstream and reach other organs, such as the kidneys, where it can damage the glomerular endothelial cells and cause hemolytic uremic syndrome (HUS), a life-threatening condition characterized by hemolytic anemia, thrombocytopenia, and acute renal failure.

Shigella dysenteriae is a highly pathogenic bacterium that can cause severe disease even with a low infectious dose (<100 bacteria). The pathogenicity of Shigella dysenteriae depends on its ability to adhere to, invade, replicate in, and spread among the colonic epithelial cells, as well as its production of Shiga toxin that can cause systemic complications. The clinical manifestations of shigellosis will be discussed in point 4.

Shiga toxin is a potent exotoxin produced by S. dysenteriae type 1 and some strains of E. coli. It belongs to the family of AB toxins, which consist of an enzymatically active A subunit and a binding B subunit. The B subunit is responsible for attaching the toxin to the host cell surface, while the A subunit is responsible for inhibiting protein synthesis and causing cell death.

Shiga toxin binds to a specific glycolipid receptor called globotriaosylceramide (Gb3) that is present on the surface of intestinal epithelial cells, endothelial cells, and renal tubular cells. The toxin is then internalized by endocytosis and transported to the endoplasmic reticulum (ER), where it dissociates into its A and B subunits. The A subunit is then translocated to the cytoplasm, where it cleaves a specific adenine residue in the 28S rRNA of the 60S ribosomal subunit. This prevents the binding of aminoacyl-tRNA to the ribosome and halts protein synthesis. As a result, the affected cells undergo apoptosis (programmed cell death) and release inflammatory cytokines.

The main target of Shiga toxin is the intestinal epithelium, which causes extensive damage and ulceration. This leads to bloody diarrhea, abdominal cramps, and fever, which are the typical symptoms of shigellosis. However, in some cases, Shiga toxin can also enter the bloodstream and reach other organs, such as the kidneys and the brain. This can cause severe complications, such as hemolytic uremic syndrome (HUS) and neurological disorders.

HUS is a life-threatening condition that is characterized by hemolytic anemia (destruction of red blood cells), thrombocytopenia (low platelet count), and acute kidney injury. It occurs when Shiga toxin damages the endothelial cells that line the blood vessels in the kidneys, causing them to become inflamed and leaky. This triggers the activation of platelets and coagulation factors, resulting in microthrombi (small blood clots) that block the blood flow to the kidneys. The reduced blood supply causes ischemia (lack of oxygen) and necrosis (tissue death) of the renal tubules, leading to impaired kidney function and urine output. The damaged red blood cells also release hemoglobin into the urine, giving it a dark color.

Neurological disorders can also occur as a result of Shiga toxin-induced damage to the brain cells. These include seizures, coma, stroke, encephalopathy (brain dysfunction), and cerebral edema (swelling of the brain). The exact mechanism of how Shiga toxin affects the nervous system is not fully understood, but it may involve direct cytotoxicity or indirect effects mediated by inflammatory cytokines.

Shiga toxin is one of the most virulent factors of S. dysenteriae type 1 and is responsible for most of its clinical manifestations. It can cause severe damage to various tissues and organs in the body, especially the intestine and the kidneys. Therefore, early diagnosis and treatment are essential to prevent life-threatening complications.

Shigella dysenteriae infection can cause two main clinical syndromes: shigellosis and hemolytic uremic syndrome (HUS).

Shigellosis

Shigellosis is a form of bacterial dysentery that is characterized by:

• Abdominal cramps

• Diarrhea

• Fever

• Bloody stools

The clinical signs and symptoms of the disease appear 1 to 3 days after the bacteria are ingested. Shigella initially colonize the small intestine and begin to multiply within the first 12 hours. The first sign of infection (profuse watery diarrhea without histologic evidence of mucosal invasion) is mediated by an enterotoxin. However, the cardinal feature of shigellosis is lower abdominal cramps and tenesmus (feeling the need to pass stool even after having emptied the bowel), with abundant pus and blood in the stool. It results from the invasion of the colonic mucosa by the bacteria. Abundant neutrophils, erythrocytes, and mucus are found in the stool.

Infection is generally self-limited, although antibiotic treatment is recommended to reduce the risk of secondary spread to family members and other contacts. Asymptomatic colonization of the organism in the colon develops in a small number of patients and represents a persistent reservoir for infection.

Hemolytic Uremic Syndrome (HUS)

Hemolytic-uremic syndrome (HUS) is a group of blood disorders characterized by low red blood cells, acute kidney failure, and low platelets. HUS can occur after an S. dysenteriae type 1 infection. Convulsions may occur in children; the mechanism may be related to a rapid rate of temperature elevation or metabolic alterations and is associated with the production of the Shiga toxin. It is usually complicated by severe dysentery, intravascular volume depletion, and cardiovascular collapse and has a higher morbidity and mortality rate than HUS associated with E. coli.

Shigellosis is the term used to describe the infection caused by Shigella bacteria. It affects the digestive system and causes diarrhea, fever, stomach pain, and cramps. In some cases, the diarrhea may be bloody or contain mucus or pus. The symptoms usually appear 1 to 3 days after exposure to the bacteria and last for 5 to 7 days.

Shigellosis is usually a mild infection that can be treated at home by drinking plenty of fluids, especially electrolyte solutions, to prevent dehydration. However, some people may develop severe or prolonged symptoms that require medical attention. These include:

• Dehydration: This can occur when the fluid loss from diarrhea is not replaced adequately. Signs of dehydration include dry mouth, thirst, reduced urine output, dizziness, and weakness.

• Dysentery: This is a severe form of diarrhea that involves blood, mucus, or pus in the stool, along with abdominal pain, fever, and tenesmus (straining to defecate). Dysentery can lead to complications such as intestinal perforation, toxic megacolon (dilation of the colon), and sepsis (blood infection).

• Hemolytic uremic syndrome (HUS): This is a rare but serious complication that occurs when the Shiga toxin produced by some strains of Shigella damages the red blood cells and the kidneys. It causes hemolytic anemia (low red blood cell count), thrombocytopenia (low platelet count), and acute kidney failure. HUS can also affect other organs, such as the brain and the heart.

People who are at higher risk of developing severe or complicated shigellosis include:

• Young children

• Elderly people

• Pregnant women

• People with weakened immune systems (such as those with HIV/AIDS, cancer, diabetes, or malnutrition)

• People who travel to areas with poor sanitation or hygiene

People who have shigellosis may benefit from antibiotic treatment to reduce the duration and severity of symptoms and to prevent the spread of infection to others. However, some strains of Shigella are resistant to certain antibiotics, so it is important to consult a doctor before taking any medication. The doctor may test a stool sample to confirm the diagnosis and to choose the appropriate antibiotic. Some of the commonly used antibiotics for shigellosis include:

• Azithromycin (Zithromax)

• Ciprofloxacin (Cipro)

• Sulfamethoxazole/trimethoprim (Bactrim)

Antidiarrheal drugs (such as loperamide) are not recommended for shigellosis, as they may worsen the condition by delaying the elimination of the bacteria and toxins from the body.

The best way to prevent shigellosis is to practice good hygiene and sanitation measures, such as:

• Washing hands frequently with soap and water, especially before eating or preparing food, after using the toilet or changing diapers, and after contact with animals or sick people

• Avoiding drinking untreated water or using ice made from untreated water

• Avoiding eating raw or undercooked food, especially shellfish, vegetables, and fruits that may be contaminated with fecal matter

• Avoiding sharing personal items such as towels, cups, or utensils with others

• Cleaning and disinfecting surfaces and objects that may be contaminated with fecal matter

• Avoiding sexual contact with someone who has shigellosis or has recently recovered from it

Hemolytic uremic syndrome (HUS) is a rare but serious complication of S. dysenteriae infection that affects the blood vessels, especially those in the kidneys. HUS can cause:

• Hemolytic anemia: a condition where red blood cells are destroyed faster than they can be replaced

• Thrombocytopenia: a condition where platelets, which help with blood clotting, are low

• Acute kidney injury: a condition where the kidneys fail to filter waste and fluid from the blood

HUS usually occurs after a few days of severe diarrhea, often bloody, caused by toxin-producing S. dysenteriae. The Shiga toxin can damage the lining of the blood vessels and cause clots to form, blocking the blood flow to the kidneys and other organs. HUS can also occur due to genetic mutations, autoimmune disorders, pregnancy, or certain medications.

The symptoms of HUS may include :

• Pale skin

• Fatigue

• Weakness

• Bruising or bleeding easily

• Decreased urine output or dark-colored urine

• Swelling of the face, hands, feet, or body

• High blood pressure

• Fever

• Abdominal pain

• Vomiting

• Diarrhea

• Confusion

• Seizures

• Coma

HUS is a medical emergency that requires hospitalization and intensive care. The treatment of HUS depends on the cause and severity of the condition but may include the following:

• Fluid and electrolyte replacement: to prevent dehydration and correct imbalances in the blood

• Blood transfusions: to increase the number of red blood cells and platelets in the blood

• Kidney dialysis: to remove waste and fluid from the blood when the kidneys are not working properly

• Plasma exchange: to remove harmful antibodies or toxins from the blood and replace them with healthy plasma from donors

• Eculizumab or eculizumab: to block the activity of a protein called complement that can damage the blood vessels in some cases of HUS

• Antibiotics: to treat bacterial infections that may cause or complicate HUS, but not routinely used for S. dysenteriae infection as they may increase toxin release

The prognosis of HUS varies depending on the cause, age, and overall health of the patient. Most children with diarrhea-associated HUS recover completely with supportive care, but some may have permanent kidney damage or other complications. Adults with HUS have a higher risk of death or chronic kidney disease. Early diagnosis and treatment can improve the outcome of HUS.

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