![]() ![]() Thus, LPS represent the main surface antigens (O-antigens) of Gram-negative bacteria. Within this outer membrane, LPS are assembled in the outer leaflet and are, therefore, located at the interface between the bacterial cell and its aqueous environment. Therefore, it appears that LPS are essential for bacterial survival, their vital role being based on their participation in the proper organization and function of the bacterial outer membrane. Bacterial mutants with defects in early steps of LPS biosynthesis are not viable. Of these macromolecules, LPS are of particular microbiological, immunological, and medical significance. Gram-negative bacteria, which include many human pathogens such as Escherichia coli, Haemophilus influenzae, Vibrio cholerae, Pseudomonas aeruginosa, and Chlamydia pneumoniae, express at their surface various amphiphilic structures including the capsular antigens, lipoproteins, the enterobacterial common antigen, and the lipopolysaccharides (LPS). Rietschel, in Comprehensive Natural Products Chemistry, 1999 3.09.1 Introduction coli (NMEC), or the capsule responsible for the mucoid morphology of Klebsiella pneumoniae. 77–79 Capsules from certain strains contribute particular pathogenic features-for example, the K1 capsule, implicated in neonatal meningitis–associated E. 75, 76Įnterobacterial capsules can help the organism survive in human serum by avoiding phagocytosis. For example, mice deficient in TLR4 fail to control gram-negative infection, and TLR4 polymorphisms in humans are associated with more severe gram-negative infection. This inflammatory immune response is responsible for septic shock but is also critical to host recovery. The TLR4-MD2 complex activates NF-κB by the MyD88 pathway to initiate transcription of proinflammatory cytokines including tumor necrosis factor (TNF), chemokines, and major histocompatibility complex (MHC) receptors. LPS, often bound to the host acute-phase protein LPS-binding protein (LBP), binds to CD14, where lipid A is recognized by the host pattern recognition receptor Toll-like receptor 4 (TLR4). ![]() coli alone featuring more than 170 different O-antigen serotypes. Genes responsible for O antigen synthesis are subject to interspecies lateral transfer, with E. The repeating oligosaccharide-or O antigen-attached to the LPS core are highly variable and, again, are the basis of Kauffman O:K:H serotyping. The core oligosaccharide is composed of a pair of 8-carbon sugars known as KDO linked to lipid A, which are in turn linked to additional sugars, forming a branched chain. The acyl groups of lipid A are inserted into the outer leaflet of the outer membrane. Lipid A is composed of a β-1,6-disaccharide of glucosamine that is phosphorylated and substituted with saturated hydroxylated acyl chains. 72 The three major domains of LPS are the lipid A-or endotoxin-backbone, the core phosphorylated oligosaccharide, and the repeating oligosaccharide side chains. LPS has different chemical compositions depending on the organism, with varying biologic activity and potency. LPS is an essential component of the outer membrane of all gram-negative bacteria that can also function as a virulence factor. Bennett MD, in Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, 2020 Lipopolysaccharide and Capsules ![]()
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