Lipopolysaccharide Biosynthesis Pathway
Bacterial cells outnumber human cells in the human body, but they all are not the same. Laboratory testing is performed to differentiate them into different species with different characteristics, using several aspects of microbiology and biochemistry. To identify different types of bacteria, microscopy has to be done. Since bacteria are colorless and transparent, microscopy will not give a complete detailed aspect of the bacteria without staining them in special inks in a procedure called Gram staining.
Gram staining contains different chemicals that the bacteria will react to and change color depending on their cell wall type. When the bacteria stains purple on the stain, it is said to be Gram-positive since it allows the primary stain of the Gram stain (methylene blue) to pass through its much thinner cell wall that lacks the lipopolysaccharides. On the other hand, if the bacteria appear pink on a microscope, it is said to be Gram-negative since it only picked up a secondary stain that is part of the Gram stain called safranin. On the cell wall, there are components called peptidoglycans which comprise Gram-positive bacteria and lipopolysaccharides, which comprise Gram-negative bacteria.
The lipopolysaccharides of the Gram-negative bacteria are mainly found in the outer membrane layer of the bacteria and itself it is a type of toxin called an endotoxin. It contains a water-insoluble component called Lipid A which our body recognizes as a foreign molecule and initiates steps to detoxify it, triggering inflammation. It is, therefore, best to keep levels of this harmful toxin known as lipopolysaccharide as low as possible in our blood circulation. So how are endotoxins formed by Gram-negative bacteria?
Lipopolysaccharide contains different components that determine how it causes sickness, and all these components are formed in different pathways. The components are O-antigen, lipid A, and core oligosaccharides. Lipid A is one of the most toxic components of endotoxins which triggers the body to produce chemicals (cytokines) that induce inflammation.
Bacteria endotoxins trigger different reactions in our body, depending on
concentration and species. Usually, Gram-negative bacteria such as Bacteroidetes can coexist with our microbiome and immune system and have positive benefits to our health in the right populations. Bacteroidetes populate our digestive tract shortly after birth and may help to train our immune system in our infancy, because of minor reactions to the endotoxins they produce. Bacteroidetes also help to break down protein into amino acids for us so that they are easily absorbed. However, when a person has an overgrowth of Bacteroidetes (population greater than 25% of their total intestinal microbiome in most cases), intestinal inflammation, bloating from excessive protein fermentation, and leaky gut (Bacteroidetes can start to digest the mucosal barrier when overgrown) may occur.
Lipopolysaccharides form the outer layer of the Gram-negative bacteria. The outermost layer of the lipopolysaccharide layer is composed of O-polysaccharide, followed by the core polysaccharide, and finally, lipid A, which can severely trigger the immune system and cause excessive inflammation.
- Lipid A
Lipid A is the innermost component of endotoxin and is made up of glucosamine disaccharide units that are phosphorylated and has a very long chain of fatty acids attached to it.
- Core Oligosaccharide
Core oligosaccharide contains two components, namely ketodeoxyoctanoic acid and another sugar called heptose, which is linked to one another by lipid A.
- O polysaccharide (O-antigen)
O polysaccharide is the outermost layer of lipoprotein, and it extends from its core. It is composed of sugars and interacts directly with the cells of the person/host.