LPS are large, intricate molecules found in nature, also known as lipoglycans due to their lipid and sugar components. They are amphipathic, possessing both water-attracting (hydrophilic) and water-repelling (hydrophobic) regions, which contributes to their diverse roles in biological systems.
Primary Location: Gram-Negative Bacteria
LPS are characteristic components of the outer membrane of gram-negative bacteria. They are embedded within this outer layer, exposed to the external environment, and contribute significantly to the bacterial cell’s structural integrity and protection from external threats.
The structure of LPS consists of three distinct regions: Lipid A, a core polysaccharide, and the O-antigen. Lipid A is the hydrophobic portion embedded in the outer membrane, serving as an anchor for the entire molecule. It is the most conserved part of LPS.
The core polysaccharide is a short chain of sugars that connects Lipid A to the O-antigen. Extending outwards from the core polysaccharide is the O-antigen, a highly variable chain of repeating oligosaccharide units, useful for identifying specific bacterial strains.
Common bacteria like Escherichia coli and Salmonella possess LPS as a major component. These thermostable molecules are a defining feature of gram-negative bacteria, the only organisms known to naturally produce LPS.
LPS in the Human Body
LPS, originating from gram-negative bacteria, are consistently present in the human body, primarily due to commensal bacteria in the gut. These bacteria are part of the gut microbiota, where their LPS are typically confined within the intestinal lumen. The gut lining acts as a barrier, preventing widespread entry of LPS into the bloodstream.
However, LPS can enter the bloodstream under specific circumstances. During severe bacterial infections, a significant amount of LPS can be released into the circulation. Disruption of the gut barrier, often called “leaky gut,” can also facilitate LPS passage from the intestine into the bloodstream, resulting from factors like inflammation or certain medical conditions.
Once in the bloodstream, LPS can be detected in various bodily fluids. Its presence in the blood, known as endotoxemia, signifies a breach of the body’s containment mechanisms and often indicates an underlying issue like infection or compromised barrier function.
Impact on Health
When LPS enters the bloodstream, it acts as a potent “endotoxin,” triggering a strong immune response. The body’s immune cells possess specific receptors, such as the CD14/TLR4/MD-2 complex, that recognize Lipid A, the endotoxic component of LPS, initiating a cascade of events to eliminate the perceived threat.
Binding of LPS to these receptors on immune cells leads to the release of pro-inflammatory molecules like cytokines and chemokines. This contributes to systemic inflammation, a widespread immune reaction. Common symptoms include fever, chills, and general malaise.
In severe cases, uncontrolled endotoxemia can progress to sepsis, a life-threatening condition caused by the body’s overwhelming response to infection. Sepsis can lead to widespread inflammation, tissue and organ damage, and a dangerous drop in blood pressure. If unchecked, this can escalate to septic shock, a severe form of sepsis characterized by dangerously low blood pressure and organ dysfunction, which can be fatal. The body’s ability to inactivate LPS through enzymes is important for restoring homeostasis after exposure.