Endotoxin is a type of toxic substance or a pyrogen released by the bacteria which is located inside the bacterial cell. Endotoxins are also components of the cell walls of the gram-negative bacteria. The most common examples of gram-negative bacteria include E. coli and K. pneumonia whereas that of endotoxin is lipopolysaccharide alias LPS.
Exotoxins are bacterial toxins that are either secreted by the bacteria or are released upon their death similar to endotoxins. The major damage caused to the host cells by exotoxins is by the disruption of cellular homeostasis or by the destruction of the cells as a whole because of their high potency. For example, cholera toxin is an exotoxin produced by the bacteria V. cholerae.
Table representing the difference between endo- and exotoxins
|Basis of differentiation||Endotoxin||exotoxin|
|Cellular location||Cell wall of bacteria||Secretion from within the bacterial cell via various mechanisms|
|Immune reactions||Fever, distress and sometimes death||Swelling, rashes on skin, fever|
|Host immune target cells||Granulocytes, macrophages, endothelial cells||Somatic cells|
|Chemical composition||Carbohydrates||Proteins and polypeptides|
|Fever induction||Yes||Lesser extent|
|Molecular weights||>100 kDa||50 – 1000 kDa|
|Strain specificity||Gram negative bacteria||Both gram positive and negative bacteria|
|Conversion to toxoids||No||Yes|
Endotoxins. As already mentioned, they are found as integral components of the outer cell walls of the gram-negative bacteria. These cell walls of gram-negative bacteria cover the plasma membranes of these bacteria and help provide them an extra covering advantageous to combat and survive the harsh environments.
Exotoxins are mostly proteins or polypeptides. As is evident from their proteinaceous nature, they are required to be synthesized inside the bacterial cell and then secreted to perform their toxic reactions. Moreover, most of them act on locations or tissues which are far away from the site of bacterial invasion which necessitates their secretion and travels through the bloodstream to their respective sites of actions.
Lipopolysaccharide is the key component of the cell wall of the gram-negative bacteria is also majorly responsible for eliciting the immune response of the host organism. It is also associated with inciting septic shock in animals. The sequence of events after endotoxins are released in the body include fever, physiological distress, and severe reactions, death can also happen. Moreover, the three types of cells through which endotoxins incite immune response are granulocytes, macrophages, and endothelial cells.
The major targets of host cells through which exotoxins incite an immune response are somatic cells. The exotoxins directly bind with the antibodies presented on the surfaces of these somatic cells. Their binding with the antibody presenting cells also prevents their invasion inside the host cells. In this way, exotoxins also behave as antigens. By binding with the antibodies and forming an antigen-antibody complex, these cells are targeted for destruction by the host immune response.
The other way through which exotoxins can act is via binding with the exotoxin specific receptors present on the host cell surface. By this, the protein synthesis is inhibited and the cell death occurs. Moreover, the host responses can include swelling, redness, and fever in most common cases.
It is a heteropolymer of LPS which can be divided into three constituent elements: lipid-A and Antigen-O. Lipid A makes the core oligosaccharide of the LPS whereas an O-antigen which is O specific oligosaccharide. Further dissection shows that lipid A is composed typically of two glucosamine units attached with beta linkage and contains linked acyl groups too. On the other hand, Antigen-O is made up of repeating units of 3-5 sugars, with individual chains having lengths of up to 40 repeating units.
These are most often protein and polypeptides. These can be further divided into subunits – most commonly A and B. In such cases, B subunits act as receptors and help facilitate binding of the toxin to the host cell while making way for the subunit A to be released into the cytoplasm.
Endotoxins show high and strong resistance against heat inactivation treatments. If dry heat is used, it requires 30 minutes of 250 degrees Celsius for their inactivation. But studies have shown that hydrothermal processing completely destroys endotoxins at just 130 degrees Celsius for 60 minutes.
Since exotoxins are mostly proteins and polypeptides in nature, they require fewer temperatures for their denaturation. Also, since most of these work on body temperatures of 37 degrees Celsius, these are often completely denatured on temperature above 40 degrees Celsius.
Since both are toxins for the body, both are believed to incite fever to some extent with endotoxins being more potent than exotoxins
Molecular weights range
Also known as lipoglycans, LPS molecules are large in size. Due to their large sizes, they also are high molecular weight compounds. Typical molecular weights of endotoxins are greater than >100,000 Daltons.
Since exotoxins are mostly proteins or polypeptide molecules, therefore their weights fall in the typical ranges of proteins and polypeptides. For example, most of the exotoxins range in their molecular weights from 50,000 – 1,000,000 Daltons.
Since endotoxins are large molecules of carbohydrate origin, and have shown considerable temperature tolerance to denaturation, they are more stable than exotoxins towards denaturation. Also, the temperatures at which exotoxins denature would not usually work for endotoxins because of their requirements of high temperatures for that.
Due to their proteinaceous nature, they are more prone to denaturing at slightly high temperatures than the physiological temperatures. Also, various denaturing agents, the most common example of which is a detergent, also effectively denatures exotoxins since they function to disrupt the protein structure thus denaturing them.
Since endotoxins are integral components of the cell walls of the gram negative bacteria, they are associated with only gram negative bacteria.
As exotoxins are secreted toxins, they are not specified with any bacterial strain and can be associated with any type of bacteria secreting them. These can include both gram positive and gram negative bacteria.
An antigenic substance is a toxic substance which has the ability to incite an immune / antigenic response in the host organism. Endotoxins are antigenic compounds capable of creating an antigenic response in the host but they are not able to be converted into toxoids – inactivated substances having the potential to be used as vaccines.
Similar to endotoxins, exotoxins are also capable of inciting the immune response of the host. But since they are protein in nature, their denatured or inactivated forms are usually made into toxoids which can then be used as vaccines.