Introduction:
Shiga toxins are potentially harmful toxins transmitted from animals to humans, primarily through water contamination or food with infected feces. When this toxin is present in the body, it is seen to have numerous delirious health effects due to the interaction of the toxic substances with both the blood and, in turn, the bodily organs. The impact of Shiga toxins on kidneys is very prominent, as it creates an overload on kidney function, affecting filtration and excretion.
What Is Shiga Toxin?
Shiga toxin is a very virulent toxin released from the bacteria known as Shigella dysenteriae or Escherichia coli, which was initially discovered in the nineteenth century. This is considered to be a very dangerous or potent bacterial infection because of its ability to cause uremic syndromes due to the breakdown of the blood cells or blood-filled diarrhea. These toxins show different types of cell toxicity with multiple enzymatic responses. On a broader scale, these Shiga toxins are known as one of the most poisonous biological substances and are transmitted from animals to humans through fecal contamination.
How Do Shiga Toxins Interact with the Blood?
When in contact with the body, the Shiga toxins primarily affect the blood; this is considered a severe and complex interaction, and every individual blood cell breakdown causes hemolysis.
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Red Blood Cells: During HUS, fragmented red blood cell count increases, leading to non-immune hemolytic anemia. Here, the red blood cells break apart mechanically when they travel through partially blocked capillaries, due to which oxidative damage stiffens RBC membranes. However, the exact process causing the breakdown of the red blood cells is unknown. Hemolysin is a potent factor encoded in plasma due to its production by E. coli.
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White Blood Cells: The Shiga toxins act differently on different white blood cells, and they are:
Monocytes: It has not been demonstrated that monocytes aid in the circulatory transmission of toxins to target cells, even though Shiga toxins can bind to, activate, and create platelet-monocyte complexes with clot-forming (prothrombotic) qualities. However, biopsies from patients with HUS show that monocytes are most likely drawn to the kidneys, showing elevated levels of monocytic protein ( monocyte chemoattractant protein-1).
Neutrophils: Activation of neutrophils occurs during Shiga infections.The Shiga toxins may accelerate the proliferation of neutrophils, causing the discharge of myeloid lineage cells from the bone marrow, which in turn may cause neutrophilia. The toxic substances present have also been shown to affect the migration of neutrophils. These rotating neutrophils in the system degranulate, generating reactive oxygen substances and enzymes like proteases.
Platelets: A decrease in platelet count in the case of Shiga toxin-associated kidney diseases like HUS is a prevalent scenario. Numerous mechanisms can cause thrombocytopenia, including the consumption of platelets in microthrombi on the surface of damaged endothelium, platelet aggregation, and deposition on endothelial cells due to a direct interaction between Shiga toxin virulence factors and platelets, activated by circulating chemokines or other circulatory platelet aggregating factors.
How Do Shiga Toxins Interact with the Kidney?
The Shiga toxins that interact with various cells of the kidney and they are:
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Specialized Epithelial Cells: These cells, also called podocytes, are one of the main cells in the kidney filtration seen in the diaphragm, filtering the blood components. These podocyte changes eventually lead to glomerular diseases involving the capsule and basement membrane. A defective podocyte causes improper urine filtration, resulting in proteinuria (a clinical condition characterized by the expulsion of protein in urine).
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The glomerular cells.
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The extraglomerular cells.
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The endothelial cells.
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Cells of the proximal tubules.
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Ductal cells.
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Cells of the distal tubules.
The components of the Shiga toxins act on the body by binding with the cholesterol in the lipid rafts of the cell, incubating in the intestine cells.
What Is the Kidney’s Response to Shiga Toxins?
The reaction of the kidney to the Shiga toxins occurs as a condition called hemolytic syndrome.
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Hemolytic Uremic Syndrome (HUS): Hemolytic uremic syndrome (HUS) is a collection of clinical conditions marked by low platelet and red blood cell counts along with acute kidney injury. Here, the main cause of HUS is clot-forming conditions of the micro blood vessels, with the cause mainly being damage to endothelial cells in microvessels (venules, capillaries, and arterioles). Escherichia coli, which produces Shiga toxin (STEC), is the main culprit responsible for typical diarrhea-associated HUS. The other STEC causes include medications, malignant hypertension, and other infections, leading to frequent causes of atypical HUS (aHUS). The incubation period of STEC is about three to eight days to incubate within the system. After this, it is clinically seen as watery diarrhea and is a normal symptom of STEC. But although watery diarrhea is seen, three to five days later, the diarrhea turns bloody, associated with severe abdominal pain along with nausea and vomiting. Following this, within two to fourteen days, a visible reduction in the platelet count is seen, along with acute kidney infection. The other nonrenal symptoms include neurological symptoms, inflammation of the pancreas, necrosis of the intestinal cells or perforation, gangrene of the finger or toe, ulcerative necrotizing skin lesions, heart attacks (myocardial infarction), ischemic cardiomyopathy (a clinical condition characterized by depletion of heart cells due to poor blood supply, affecting about 20 percent of individuals.
However, as of now, there is no vaccination for STEC infection in humans. Various platforms and methods are used as the foundation of vaccines against the E.coli infection. The chimeric proteins from the attenuated bacteria (which comprise detoxified Stxs (Shiga toxins), nontoxic Stx B subunit, peptides, etc, show a DNA containing nontoxic bacterial ghost cells produced from the E.coli strain, and polysaccharides are some of the antigens that are delivered in vaccinations. Several adjuvants, including other attenuated toxins, can be added to vaccinations to increase their effectiveness.
Conclusion:
However, most research shows a connection between antibiotics and HUS, with small sample sizes and various antibiotic treatment regimens over time. Many of the findings need to be more consistent. Here, the use of antibiotics was not linked to an increased incidence of HUS; however, significant usage is seen to be associated with it. Antibiotics are therefore not advised for those with STEC infections as they can compromise the body’s immunity over the period, leading to the fact that patients who get sick much faster are more likely to develop HUS, where consumption of antibiotics complicates the link between HUS and antibiotic use.
