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Hi everyone, it's good to have you here today, and in this post, I will be discussing bacteria endotoxins and exotoxins. To understand this topic, we need to first identify which bacteria produce endotoxins and which bacteria produce exotoxins. In my last post, I explained that gram-negative bacteria possess an outer membrane, and endotoxin is present in the outer membranes of the bacteria. This means that gram-negative bacteria are the group of bacteria that possess endotoxin and like I said in my previous post that the toxin is called lipopolysaccharides (I dare you to say that name fast 7 times, you might lose a tooth). Don't forget in your bacteriology or microbiology, you were told that lipopolysaccharides components are made up of the bacterial chromosome and are of three parts, the lipid A, the core polysaccharide, and the O antigen (I wrote that in my previous post if you could just go back and read it). In case you feel tired to click that mouse to find my previous post, do not worry I will help explain the Lipopolysaccharide to you in full (awn! maybe not in full but you will like it).

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Your regular gram negative bacteria cell wall will be something like this; the Capsule and slime layer, the outer membrane, the peptidoglycan layer, the inner membrane then the bacteria DNA in the endoplasm which has ribosomes. The lipopolysaccharide is found within the outer membrane of bacteria. Lipid A is directly fixed to the outer membrane, and it is the immunogenic component of the lipopolysacharide which causes the immune system of the host/patient to be triggered (it is responsible for white blood cells to release cytokines), followed by the Lipid A is the core polysaccharide but this part isn't really responsible for virulence, we could say it is responsible for holding the Lipid A to the O-Antigen. The O-antigen is the antigenic part of the lipopolysacharide and it triggers the antibodies to react to it.

Lipid A of the lipopolysacharide when in the host, activates macrophages,by binding to the microphage protein Toll-like receptor 4 (TLR-4), CD-15 and other proteins, causing the release of cytokines (interleukin-1, interleukin-6, TNF-alpha, and nitric oxide), stimulating the hypothalamus of the brain to cause increase in the body temporature of the host causing fever. The cytokines such as TNF-alpha and Nitric oxide causes vasodilation and capillary permeability of the blood vessels, causing hypotension or low blood pressure which could over a long time lead to failures or important organs such as the kidney, liver, heart, and the lungs and this could lead to septic shock. That's not all, let's continue with what the lipid A can do. The Lipid A activates the complement system which are innate immune proteins produced by the liver, as the complement proteins would bind to the bacteria as they try to destroy the bacteria but in the process, some proteins such as the C3a and the C5A which have inflammatory properties which can activate basophils to produce histamine which icreases vasodilation and increased permeability which can cause edema and hypotension, they can also stimulate neutriphils causing chemotaxis where they can cause inflammatory responses. Finally, they activate the tissue factor (Factor III) within the coagulation cascade. Factor III activates factor VII which activates factor X which activates thrombin which converts fibrinogen to fibrin which is important and clot formation. When the factor III is activated, it can lead to clotting which can be widespread and can lead to the depletion of coagulation proteins as they are used up for clotting, leading to Disseminated Intravascular Coagulation.

That discussed, I hope it wasn't too much to handle. let me quicly do a rundown. Endotoxins is found in outer membrane of gram negative bacteria. lipopolysaccharide is the endotoxin, and it has three parts, two of which trigger the immune system while the other which is the middle part holds the two virulence and antigenic part together. It is important to know that since they are endotoxins, the toxin is released as a result of a lysing of the bacteria. Gram negative bacteria that possess endotoxins are E-coli, Salmonella, Neseria Meningitidis, and  Klebsiella spp.

Let's discuss Exotoxins. Exotoxins are found in what type of bacteria? I was expecting you to say gram positive bacteria, you know like that word and opposite you did in elementary school. Anyway, exotoxin is found in both gram positive and gram negative bacteria. The toxins are made in the proteins of the bacteria cell and expelled out of the cell. Exotoxin acts as super antigen binding between the antigen presenting cell and a T-helper cell of the host causing an enhancement between the two cells causing the T-cells to release cytokines which causes inflamatory responses. The exotoxins also exert themselves into the cell, damaging the cells and parts of the cell membrane. They can also use their AB toxins which helps them get into the cells of their host and inhibits protein synthesis inside the cell. They can also pocess injectosome which will eject its toxins into the cell when it has been taken up by the cell. Bacteria such as Staphylococcus aureus possesses Toxic Shock Syndrome Toxin which acts as super antigen binding between the antigen presenting cell and a T-helper cell of the host causing the T-cells to release cytokines which causes inflamatory responses. It also releases Enterotoxin. Other bacteria that follow this same proccess are Streptococcus Pyogene which possesses the Erythrogenic toxin. Streptococcus Pyogene also exerts that destructive effect on the host cell through a toxin called streptolysin protein. Leukocidin proteins are another one that also exerts that destructive effect on the cell. This is released by Staphylococcus aureus. Clostridium also releases alpha toxins which also exerts damaging effects on the cell of the host. Bacteria such as psuedomonas aeriginosa which releases exotoxin type A, Shigella which releases Shiga toxin, which Vibrio Cholerae releases Cholera toxin and so on, and they all act by using their AB toxins to help them get into the cells of their host and inhibits protein synthesis inside the cell. 

#### <center>Conclusion</center>
While endotoxin is synonimous to gram negative bacteria, both gram positive and gram negative bacteria can possess exotoxin. Both toxins are responsible for triggering the immune response, and causing inflammation. While one is inside the cell and is released when lysed, the other is produced from the cell and released from the bacteria. Thanks a lot for reading. I hope you enjoy the rest of your day.


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<center>**Reference**</center>
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3916377/

https://www.bionity.com/en/encyclopedia/Endotoxin.html

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2365449/pdf/MI-02-S21.pdf

https://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-019-1564-7

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6091223/

https://ccforum.biomedcentral.com/articles/10.1186/cc13110 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2569852/