Differences Between Exotoxins And Endotoxins

Endotoxins and exotoxins are both created by bacteria.

Differences Between Exotoxins And Endotoxins

Endotoxins and exotoxins can both seem to be similar, but they are both created and released in different ways, and have different effects.

Exotoxins are notoriously more potent than endotoxins, although both are known for their toxicity. 

What Are Endotoxins?

The vast majority of endotoxins as we describe them today are examples of lipopolysaccharides.

The term endotoxin has become effectively synonymous with lipopolysaccharides (LPS), although there are still some other endotoxins that have no relation to LPS.

LPS is the key component in the outer membrane of bacteria – it not only plays a major part in maintaining the structural integrity of the bacteria, but also serves as defense for the membrane against chemical attacks.

On most Gram-negative bacteria, the antigen LPS can be found in abundance. The outer membrane of some bacteria can be composed of up to 80% LPS.

LPS is so important to the majority or Gram-negative bacteria that they will die if LPS is removed or mutated.

This, however, is not the case with all Gram-negative bacteria. For some, LPS is a nonessential part of their system.

Early research into endotoxins led to them being thought of as toxins that were only released during the destruction of this outer membrane.

However, further research showed that the destruction of this cell wall was not necessary for the secretion of endotoxins – and that, in fact, LPS will be more often secreted as a normal physiological function of the bacteria.

Compared to exotoxins, endotoxins are generally far less potent.

A much higher dose of an endotoxin will be required to cause a disease, and a far higher amount is required for fatality.

However, this does not mean that endotoxins are incapable of causing great harm in affected hosts. For instance, the disease gonorrhea is caused by endotoxins.

Endotoxemia, which is when endotoxins can be found in the blood, can lead to septic shock.

And, despite the potency and toxicity of LPS and other endotoxins being far lower than that of exotoxins, they can still cause illness in even small amounts.

Human beings are far more likely to be sensitive and susceptible to the effects of LPS than many other animals are.

For instance, a mouse can safely handle a dose 1000 times of that which would cause a septic shock in human beings. 

LPS is a known contaminant in the pharmaceutical industry, and it is vital that steps are taken to ensure that endotoxins are not present in drug containers.

To completely break down endotoxins so that they are not harmful to humans, temperatures over 572F (300C) are required.

What Are Exotoxins?

Exotoxins are a potent type of toxin that are secreted by bacteria.

Exotoxins are generally highly potent in comparison to endotoxins – a single molecule of an exotoxin can affect a large number of cells in the host.

Much larger amounts of endotoxins are required to cause a disease in the host. Exotoxins are also far more toxic than endotoxins.

So, not only is a smaller dose of an exotoxin required to have an effect, but the effect is generally far more severe. Exotoxins can easily be fatal in microgram quantities.

The effect of exotoxins can of course vary depending on the specific exotoxin.

Their effects can be either local to the affected cells, or can have wider effects on the chemical and biological systems of the affected host.

The majority of exotoxins can have their toxicity reduced or negated by heat and chemical treatment, resulting in the production of a toxoid.

Toxoids can be used to create antitoxins, and can further be used to develop vaccines.

Many diseases and health issues are caused by the presence of exotoxins.

However, due to the fact that toxoids can be developed from exotoxins, they have found medical application in the creation of vaccines.

One of the most widely used vaccines created from toxoids derived from exotoxins is the DPT vaccine, which protects recipients against diphtheria, pertussis, and tetanus.

There is also ongoing research into the development of cancer treatments using exotoxins.

This is due to the potency of exotoxins; they can “kill” cancer cells without the need to destroy them entirely in the way that radiation therapy or chemotherapy would.

Exotoxins are mostly produced by Gram positive bacteria, but this is not exclusive. There are also Gram negative bacteria that produce examples of endotoxin.

Exotoxins are created by pathogenic bacteria as a normal part of their metabolic cycle.

Exotoxins can be attacked by the immune system of the host, which produces antibodies to combat the toxins.

However, due to the extreme potency and toxicity of many exotoxins, it is common that some exotoxins will have a fatal effect long before the antibodies produced can have any effect.

There are many different exotoxins, and they have been classified and grouped in many different ways.

For instance, they can be sorted by the organism that generates the exotoxin, or instead by the organisms that are susceptible to the effects of the toxin.

They can be further differentiated by the type of tissue that is affected by the toxin – for instance, some exotoxins target the heart, whereas others can target the brain.

And, there are many other ways that exotoxins can be grouped and classified. It’s possible that an exotoxin can have multiple names too, according to the various fields it may be studied in.

Differences Between Exotoxins And Endotoxins


Exotoxins are produced inside bacteria. The majority of bacteria that produce exotoxins are Gram-positive, although they can be produced by Gram-negative bacteria too.

This is a normal part of the growth, metabolism, and life cycle of these bacteria.

Endotoxins are present in the outer membrane of bacteria. They play an important part in maintaining the structural integrity of this membrane, and by extension the bacteria itself.

They also help to provide resistance to the outer membrane against chemical attack.


The majority of endotoxins are examples of lipopolysaccharides. These are large molecules, made up of a lipid and a polysaccharide.

The polysaccharide is composed of an inner core, an outer core, and O-antigen.

Exotoxins can be very different from each other in their chemical composition. They are all, however, composed of various proteins.


Exotoxins are typically composed of two subunits, labeled A and B. Subunit A handles catalytic activity. Subunit B bonds to an appropriate cell receptor.

LPS endotoxins are a combination of three components – the Lipid, called lipid A, O-antigen, and the core oligosaccharide.

The core is an inner and outer core that are joined by a covalent bond.



Endotoxins are generally far less potent than exotoxins. Far smaller levels of exotoxins can have a more potent effect than endotoxins.


Both exotoxins and endotoxins can be toxic. However, exotoxins are far more toxic, and in much smaller doses.

Exotoxins can affect far more cells with far lower levels of the exotoxin present, and can be fatal in doses measured in micrograms.


Both endotoxins and exotoxins contain a number of different enzymes.

Some enzymes commonly found in endotoxins include Catalase, Fibrinolysin, and IgA / IgG proteases.

Exotoxins can contain enzymes such as Neuraminidase, Hyaluronidase, Nuclease, and Collagenase.


Endotoxins are found inside the cell membrane of certain bacteria. These bacteria are always Gram-negative.

They are an important part of the structure of these bacteria, and can be up to 80% of the outer membrane of these bacteria. As such, endotoxins are only released after cell lysis.

Exotoxins are a secretion of both Gram positive and Gram negative bacteria. They are a normal, routine part of the metabolic and growth cycle of these bacteria.

Chromosomal Location

Endotoxins are located on chromosomal genes. Exotoxins are located on extrachromosomal genes – for example, plasmids.


Exotoxins are secretions of certain bacteria. They are produced in living bacteria, and are secreted out of the cell as a part of the bacteria’s normal growth and metabolism.

Endotoxins, however, are not secretions, but an important part of the cell wall of bacteria.

They are responsible for holding the bacteria together, and for defending it against outside chemical attack. They are not typically released until the cell dies, but it can occur.

Cell Lysis

As exotoxins are created as a part of process within the bacteria, and are secreted normally, cell lysis is not required for their release.

The bacteria produces these toxins while it is still alive.

However, endotoxins will not always be released without cell lysis. LPS is not always a normal secretion, and often requires the death of the cell for release.

In these cases, the outer membrane of the cell must break down for the release of LPS from the bacteria. Therefore, cell lysis is often essential for the release of endotoxins.

Heat Stability

Exotoxins are heat labile, and can often be destroyed at relatively low temperatures compared to endotoxins.

Often, temperatures of 1472F (800c) can be sufficient to kill exotoxins.

In comparison, endotoxins are heat stable, and can be more heat resistant, depending on the strain and circumstances.


Due to the nature of endotoxins, they cannot be used to develop toxoids. Therefore, no vaccines can be made from them.

However, exotoxins can be used to develop toxoids. These toxoids can be developed by the application of either heat or chemicals to the exotoxins, deactivating them.


By boiling, exotoxins can be denatured. However, endotoxins will not be denatured by boiling.


Exotoxins are extremely specific when it comes to targeting. They act on specific host cells, and can each have different mechanisms for interacting with them.

This is one reason why there are so many different ways of classifying and grouping exotoxins.

Endotoxins are less focused and specific in comparison.


Endotoxins can be detected by a Limulus lysate assay test. Exotoxins are detected by precipitation, ELISA-based methods, and neutralization.


Endotoxins do not produce antitoxins, and display weak levels of immunogenicity. By comparison, exotoxins show very high levels of immunogenicity.


On the surface, there are definitely similarities between endotoxins and exotoxins.

However, their differences allow us to not only group and classify them, but understand the mechanisms by which they take effect.

Hopefully, this simple guide to endotoxins and exotoxins has helped you to understand the differences between them!

Jennifer Dawkins