E. coli 0157:H7 Part 2 - Pathogenesis & Complications

Summary

This video explains the pathogenesis and complications of Escherichia coli O157:H7, a virulent bacterium that infects the intestines and can cause severe symptoms such as bloody diarrhea. The bacteria use fimbria to attach to intestinal cells, release Shiga toxins that disrupt protein synthesis, and damage cells. These toxins can spread to other organs, leading to serious complications like Hemolytic Uremic Syndrome (HUS), acute renal failure, and neurological issues. The video outlines the step-by-step process of infection and the severe consequences, especially for children, with potential long-term kidney damage and a 3-5% mortality rate.

Takeaways

• 😀 E. coli O157:H7 is a virulent bacteria that infects the enterocytes of the distal ileum and colon, causing bloody diarrhea and systemic complications.
• 😀 The infection begins with the bacteria using fimbriae to attach to the surface of the enterocyte in a process called fimbrial attachment.
• 😀 The bacteria then translocates a protein called TRIR (Translocated Intimin Receptor) to the enterocyte membrane.
• 😀 TRIR binds to intimin on the surface of the bacteria, allowing it to attach firmly to the enterocyte.
• 😀 Shiga toxin is released by the bacteria, binding to GB3 or GB4 receptors on the enterocyte surface.
• 😀 Shiga toxin is internalized by the cell, stopping protein synthesis and leading to cell damage and death, contributing to bloody diarrhea.
• 😀 The shiga toxin can enter circulation and travel to organs, where it can damage red blood cells, platelets, kidneys, and the brain.
• 😀 The pathogenesis of E. coli O157:H7 involves nine steps: attachment, translocation, binding, toxin release, receptor binding, internalization, cell damage, toxin circulation, and organ damage.
• 😀 A major complication of the infection is Hemolytic Uremic Syndrome (HUS), characterized by kidney microvascular damage, leading to acute renal failure.
• 😀 HUS is the most common cause of acute renal failure in children infected with E. coli O157:H7, with a mortality rate of 3-5%, and survivors may suffer permanent kidney damage.
• 😀 The shiga toxin can also cause neurological complications, such as strokes, seizures, coma, and hemiparesis, due to microthrombi in the brain microvasculature.

Q & A

What is *E. coli* O157:H7 and why is it considered a virulent bacterium?

*E. coli* O157:H7 is a pathogenic strain of *Escherichia coli* that is capable of causing severe infections. It is considered virulent because it can invade the intestinal cells (enterocytes) and release harmful toxins that damage organs, including the kidneys, brain, and red blood cells, leading to potentially fatal complications like hemolytic uremic syndrome (HUS).

How does *E. coli* O157:H7 initiate infection in the human body?

The infection begins when the bacteria attach to the surface of enterocytes using fimbriae. This is called fimbrial attachment, after which bacterial proteins (TRIR) are translocated to the enterocyte membrane, where they bind to the receptor protein intimin. This binding helps the bacteria adhere more firmly to the intestinal cells.

What is TRIR, and what role does it play in the infection process?

TRIR stands for translocated intimin receptor. It is a bacterial protein that is translocated from the bacteria to the enterocyte membrane. TRIR interacts with the intimin protein expressed by the bacterium, facilitating a stronger attachment to the enterocyte, which is crucial for the infection process.

What is the significance of Shiga toxin in the pathogenesis of *E. coli* O157:H7?

Shiga toxin is a potent toxin released by *E. coli* O157:H7 once it binds to the surface of enterocytes. The toxin binds to specific receptors (GB3 and GB4) on the cells, is internalized, and disrupts protein synthesis. This leads to cell death, contributing to bloody diarrhea and enabling the toxin to spread to other organs.

What are the consequences of Shiga toxin entering the bloodstream?

Once Shiga toxin enters the bloodstream, it can travel to various organs and cause widespread damage. It can affect red blood cells, platelets, kidneys, and the brain. In severe cases, this systemic damage can lead to life-threatening complications like hemolytic uremic syndrome (HUS), stroke, and neurological impairment.

Can you summarize the steps involved in the pathogenesis of *E. coli* O157:H7?

The pathogenesis of *E. coli* O157:H7 involves several steps: 1) Fimbrial attachment of the bacteria to enterocytes. 2) Translocation of TRIR to the enterocyte membrane. 3) Binding of TRIR to intimin on the bacteria surface. 4) Release of Shiga toxin. 5) Binding of Shiga toxin to GB3 and GB4 receptors on enterocytes. 6) Internalization of the toxin and inhibition of protein synthesis. 7) Enterocyte damage and potential death. 8) Toxin enters circulation. 9) Damage to RBCs, platelets, kidneys, and brain, potentially leading to death.

What are the primary organ systems affected by *E. coli* O157:H7 infection?

The primary organs affected by *E. coli* O157:H7 infection are the gastrointestinal system (causing bloody diarrhea), kidneys (leading to hemolytic uremic syndrome and renal failure), the brain (potentially causing neurological symptoms like stroke and seizures), and blood cells (resulting in hemolysis and thrombocytopenia).

What is hemolytic uremic syndrome (HUS), and how is it related to *E. coli* O157:H7 infection?

Hemolytic uremic syndrome (HUS) is a serious complication of *E. coli* O157:H7 infection, characterized by the destruction of red blood cells (hemolysis), low platelet counts (thrombocytopenia), and acute kidney failure. HUS is the most common cause of acute renal failure in children, with a mortality rate of 3-5%. Survivors may experience long-term kidney damage.

What role do platelets play in the development of complications in *E. coli* O157:H7 infection?

Platelets play a critical role in the development of complications like disseminated intravascular coagulation (DIC) in *E. coli* O157:H7 infection. The Shiga toxin can activate platelets, causing them to clump together and form thrombi. These thrombi can block small blood vessels in the kidneys and other organs, contributing to tissue damage and organ failure.

What neurological complications can arise from *E. coli* O157:H7 infection?

Neurological complications from *E. coli* O157:H7 infection may include strokes, seizures, coma, and hemiparesis (muscle weakness on one side of the body). These complications are caused by damage to the microvasculature in the brain, which can cut off blood supply to brain tissue, leading to neurological deficits.