Let’s investigate the potentially deadly endotoxins. Endotoxins are a substance unique to gram-negative bacteria.
Uncover how our immune system copes with endotoxins and their associated health effects in this lesson.
Suppose you were feeling ill from a bacterial infection. Chances are the doctor would prescribe an antibiotic and in a few days, you would be feeling better. But there are two main categories of bacteria: gram-positive bacteria and gram-negative bacteria. Unfortunately, gram-negative bacteria are harder to kill with antibiotics.
To make matters worse, when gram-negative bacteria are destroyed, say by antibiotics or by our immune system, they release toxins into our body called endotoxins. Endotoxins can make us very sick, and in some cases, even cause death.
Where Endotoxins Come From
Both gram-negative and gram-positive bacteria have a plasma membrane and a peptidoglycan layer in their cell wall. The peptidoglycan layer is made of a sugar and peptide chain that adds structural strength to the cell wall. However, gram-negative bacteria have characteristics that separate them from gram-positive bacteria.
The peptidoglycan layer of gram-negative bacteria is much thinner than that of gram-positive bacteria but they have an outer membrane covering it.This outer membrane contains a fatty sugar layer called lipopolysaccharide (LPS). The term lipopolysaccharide can be broken into two words: lipo (fat) and polysaccharide (sugar). Within the lipid portion of this LPS layer is lipid A, which is a dangerous endotoxin.
Antibiotics have a difficult time penetrating this outer membrane, rendering them more resistant.Gram-negative bacteria release dangerous endotoxins primarily when they are killed. This can occur when the immune system or antibiotics attack the bacteria and break down their cell walls. When the cell walls are broken, fragments of the outer membrane are released into the body, including the endotoxins. ‘Endo’ means internal or within, and, in this case, refers to the endotoxin’s existence within the outer cell membrane.This is in contrast to exotoxins, which are toxins that are secreted or released from the cell. The prefix ‘exo’, means external, implying that the toxin is excreted to the outside of the cell.
Exotoxins have the ability to be secreted from gram-positive or gram-negative bacteria at any point or they can be released when a cell dies.
Immune Response to Endotoxins
Picture your immune system playing a game of tennis and the opponent is gram-negative bacteria. The play is for the winning point and your immune system lines up to return its opponent’s volley. After a perfect swing, hitting the sweet-spot on the racket, the immune system ends up putting too much force into the hit. The ball flies out of bounds, losing its chance to win the game point. This tennis play is very similar to the way the immune system responds to endotoxins. It’s not that the immune system is not capable of handling endotoxins that can make us so ill but rather it’s that the immune system’s response is often too strong for our body to manage.
Endotoxins stimulate the release of large amounts of proteins called cytokines. Cells communicate with each other via cytokines, and these particular cytokines stimulate the activation of the immune system. They send messages to the cells in our immune system to clear the endotoxins. However, the large number of cytokines released can overwhelm the body, and become toxic in and of themselves.
This in turn releases a cascade of inflammatory events, leading to symptoms that include fever, aches, shock, and even death.
Diseases Caused by Endotoxins
Septic shock occurs when lipid A becomes systemic throughout the body. ‘Sepsis’ refers to a bacterial infection in the bloodstream and ‘shock’ refers to critically low blood pressure. Once endotoxins enter the bloodstream, our immune system’s inflammatory response leads to blood vessel damage.
As blood vessels become permeable, they lose fluid, which results in life-threatening low blood pressure. Around a half-million people develop septic shock in the United States annually and many of these cases are lethal.Unfortunately, there are many common diseases caused by gram-negative bacteria. Escherichia coli (more well known as simply E-Coli) is often found in contaminated food or water and can cause food poisoning symptoms.
Vibrio cholera grows in water and is the bacterium that causes cholera. The sexually transmitted disease gonorrhea results from bacteria called Neisseria gonorrhoeae. One of the suspected causes of the Black Death is the gram-negative bacteria called Yersinia pestis.
Gram-negative bacteria are significant in that they house an outer membrane covering in the peptidoglycan layer in their cell wall. This outer membrane is comprised of lipopolysaccharide (LPS).
Part of the LPS layer includes lipid A, which is a dangerous endotoxin. Endotoxins are released into our body when gram-negative bacteria are destroyed by antibiotics or our immune system.However, just as a tennis player who puts too much power into a hit can lose a point, it’s our immune system’s overpowering response to endotoxins that’s often the real problem. An infection of gram-negative bacteria can result in numerous diseases, as well as septic shock, which is potentially fatal.