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Lipopolysaccharides (LPS) are important outer membrane components of gram-negative bacteria. They are large amphipathic glycoconjugates that typically consist of a lipid domain (hydrophobic) attached to a core oligosaccharide and a distal polysaccharide. These molecules are also known as lipoglycans due to the presence of lipid and sugar molecules. The lipopolysaccharides are composed of: Lipid A: the hydrophobic domain, which is an endotoxin and the main virulence factor O-antigen, the repeating hydrophilic distal oligosaccharide The hydrophilic core polysaccharide The lipid A component varies from one organism to another and is essential in imparting specific pathogenic attributes to the bacteria.[1] Inherent to gram-negative bacteria, LPS provides integrity to the bacterial cell and a mechanism of interaction of the bacteria to other surfaces.[2] Most bacterial LPS molecules are thermostable and generate a robust pro-inflammatory stimulus for the immune system in mammals. Since different types of LPS are present in different genera of gram-negative bacteria, LPS is used for serotyping gram-negative bacteria.[3] More specifically, the O-antigen imparts serological distinction to the bacterial species. Also, the size and composition of LPS are highly dynamic among bacterial species. Due to its unique properties, LPS has gained considerable research focus to understand its complex structure, biogenesis, transport, and assembly. Besides, LPS is also a recognized biomarker due to its central role in host-pathogen interaction that facilitates the infection process.

LPS is a potent endotoxin that binds to cell surface receptors such as TLR4/CD14/MD2 that induce the secretion of proinflammatory cytokines, nitric oxide, and eicosanoids. The presence of LPS in the blood or interstitial fluid can lead to endotoxemia through Lipid A moiety, which can cause septic shock under an exaggerated immune response. Septic shock includes tachycardia, tachypnea, temperature modulations, and coagulation cascade activation, leading to arterial and venous dilation.[22] The resulting hypovolemia leads to cellular dysfunction as a result of inadequate tissue perfusion. Recently, a low dose of LPS exposure has correlated with autoimmune diseases and allergies, while high concentrations of LPS in the blood lead to metabolic syndrome. This increases the risk of serious diseases such as type 2 diabetes, heart disease, and liver disease. Furthermore, endotoxins are inherently responsible for the clinical manifestations of infections with Gram-negative bacterial pathogens, such as Neisseria meningitides, that cause meningococcal disease, such as Waterhouse-Friderichsen syndrome, meningococcemia, and meningitis. Specific opportunistic pathogens like Pseudomonas aeruginosa, Burkholderia cepacia complex bacteria, Helicobacter pylori, and Salmonella enterica can adapt through LPS structure-function changes to develop a chronic infection in the respiratory and gastrointestinal tract.[3] Recently, research has demonstrated that LPS induces membrane lipid disturbances, which affect cholesterol interacting proteins, lipoprotein metabolism, and membrane apo E/amyloid-beta interactions. These alterations predispose to hypercholesterolemia, dyslipidemia, and non-alcoholic fatty liver disease.[23] In some cases, the presence of LPS can interfere with the clearance of toxins from the body, linking it to neurological degeneration.[24]