Lipopolysaccharide 412942 224627817 2008-07-09T18:48:04Z 24.192.253.15 /* Lipid A */ [[Image:LPS.png|thumb|331px|Lipopolysaccharide (captions are in French)]] '''Lipopolysaccharide''' ('''LPS''') is a large [[molecule]] consisting of a [[lipid]] and a [[polysaccharide]] ([[carbohydrate]]) joined by a [[covalent bond]]. ==Functions== [[Image:Toll-like receptor pathways revised.jpg|thumbnail|right|300px|[[Toll-like receptor]]s of the [[innate immune system]] recognize LPS and trigger an [[immune response]].]] LPS is a major component of the [[outer membrane]] of [[Gram-negative]] bacteria, contributing greatly to the structural integrity of the bacteria, and protecting the membrane from certain kinds of chemical attack. LPS is an [[endotoxin]], and induces a strong response from normal animal [[immune system]]s. The only [[Gram-positive]] bacteria that possesses LPS is ''[[Listeria monocytogenes]]'', the common infective agent in [[pasteurized|unpasteurized]] [[milk]].<ref>{{cite journal | last = Wexler | first = Hannah | coauthors = Joel D. Oppenheim | year = 1979 | month = March | title = Isolation, Characterization, and Biological Properties of an Endotoxin-Like Material from the Gram-Positive Organism Listeria monocytogenes | journal = Infection and Immunity | volume = 23 | issue = 3 | pages = 845–857 | publisher = American Society for Microbiology | issn = 0019-9567 | pmid = 110684 | url = http://iai.asm.org/cgi/reprint/23/3/845?view=long&pmid=110684 | format = PDF | accessdate = 2008-04-08 }}</ref> LPS acts as the prototypical [[endotoxin]], because it binds the [[cluster of differentiation|CD14]]/[[TLR 4|TLR4]]/[[Lymphocyte antigen 96|MD2]] [[receptor (biochemistry)|receptor]] complex, which promotes the secretion of pro-[[inflammatory]] [[cytokine]]s in many cell types, but especially in macrophages. An "LPS challenge" in immunology is the exposing of the subject to an LPS which may act as a toxin. LPS also increases the negative charge of the [[cell membrane]] and helps stabilize the overall membrane structure. LPS is additionally an exogenous pyrogen (external fever-inducing compound). With the Lipopolysaccharide being of crucial importance to gram negative bacterial cells, resulting in the death of the cell if it is mutated or removed, it is therefore a prime target for future antimicrobial substances. ==Composition== It comprises three parts: * [[polysaccharide]] (O) [[side chain]]s * core polysaccharide (core oligosaccharide in genus Neisseria) * [[lipid A]] ===Lipid A=== Lipid A contains unusual [[fatty acid]]s ('e.g.' hydroxy-[[myristic acid]]) and is embedded into the outer membrane while the rest of the LPS projects from the surface. Lipid A, which is a disaccharide with multiple fatty acid tails reaching into the membrane. This is the key in the toxicity. When bacterial cells are lysed by our efficiently working immune system, fragment of membrane containing lipid A are released into the circulation, causing fever, diarrhea, and possible fatal endotoxic shock (also called septic shock). ===Core oligosaccharide=== Core oligosaccharide contains unusual [[sugar]]s (''e.g.'' KDO, keto-deoxyoctulosonate and [[heptose]]). The core oligosaccharide is attached to [[lipid A]], which is also in part responsible for the toxicity of gram-negative bacteria. ===O-antigen=== The polysaccharide side chain is referred to as the O-[[antigen]] of the bacteria. O side chain (O-[[antigen]]) is also a polysaccharide chain that extends from the core polysaccharide. The composition of the O side chain varies between different [[gram-negative]] bacterial strains. The presence or absence of O chains determine whether the LPS is considered rough or smooth. Full length O-chains would render the LPS smooth while the absence or reduction of O-chains would make the LPS rough. <ref>{{cite journal |author=Rittig MG et al |title=Smooth and rough lipopolysaccharide phenotypes of Brucella induce different intracellular trafficking and cytokine/chemokine release in human monocytes |journal=Journal of Leukocyte Biology |volume=5 |issue=4 |pages=196–200 |year=2004 |pmid = 12960272 }}</ref>Bacteria with rough LPS usually have more penetrable cell membranes to hydrophobic antibiotics since a rough LPS is more hydrophobic. <ref>{{cite journal |author=Tsujimoto H et al |title=Diffusion of macrolide antibiotics through the outer membrane of Moraxella catarrhalis |journal=Journal of Infection and Chemotherapy |volume=74 |pages=1045–1055 |year=2003 |pmid = 11810516 }}</ref> O side chains are easily recognized by the [[antibody|antibodies]] of the host, however, the nature of the chain can easily be modified by [[Gram-negative]] [[bacterium|bacteria]] to avoid detection. The structure of the core and the O-antigen is often determined by [[methylation analysis]] or [[NMR]]-spectroscopy. ==LPS modifications== The making of LPS can be modified in order to present a specific sugar structure. Those can be recognised by either other LPS (which enables to inhibit LPS toxins) or glycosyltransferases which use those sugar structure to add more specific sugars. It has recently been shown that a specific enzyme in the intestine ([[alkaline phosphatase]]) can detoxify LPS by removing the two phosphate groups found on LPS carbohydrates <ref>{{cite journal |author=Bates J.M. et al |title=Intestinal alkaline phosphatase detoxifies lipopolysaccharide and prevents inflammation in zebrafish in response to the gut microbiota|journal=Cell Host and Microbe |volume=2(6) |pages=371–382 |year=2007 |pmid = 18078689 |doi=10.1016/j.chom.2007.10.010 }}</ref>. This may function as an adaptive mechanism to help the host manage potentially toxic effects of gram-negative bacteria normally found in the small intestine. ==Variability and effect upon specificity== O-antigens (the outer carbohydrates) are the most variable portion of the LPS molecule, imparting the antigenic specificity. In contrast, lipid A is the most conserved part. However, —lipid A composition also may vary (e.g., in number and nature of acyl chains even within or between genera). Some of these variations may impart antagonistic properties to these LPS. For example [[Rhodobacter sphaeroides]] diphosphoryl lipid A (RsDPLA) is a potent antagonist of LPS in human cells, but is an agonist in hamster and equine cells. It has been speculated that conical Lipid A (eg from E coli) are more agonistic, less conical lipid A like those of Porphyromonas gingivalis may activate a different signal ([[TLR2]] instead of TLR4), and completely cylindrical lipid A like that of Rhodobacter sphaeroides is antagonistic to TLRs.<ref>{{cite journal |author=Netea M et al |title=Does the shape of lipid A determine the interaction of LPS with Toll-like receptors? |journal=Trends Immunol |volume=23 |issue=3 |pages=135–9 |year=2002 |pmid=11864841 |doi=10.1016/S1471-4906(01)02169-X}}</ref><ref>{{cite journal |author=Seydel U, Oikawa M, Fukase K, Kusumoto S, Brandenburg K |title=Intrinsic conformation of lipid A is responsible for agonistic and antagonistic activity |journal=Eur J Biochem |volume=267 |issue=10 |pages=3032–9 |year=2000 |pmid=10806403 |doi=10.1046/j.1432-1033.2000.01326.x}}</ref> ==Functions== LPS function has been under experimental research for several years due to its role in activating many [[transcription factor]]s. LPS also produces many types of mediators involved in [[septic shock]]. ==Diversity== Lipololysaccharide gene clusters are highly variable between different strains, subspecies, species of bacterial pathogens of plants and animals.<ref>{{cite journal |author=Reeves P, Wang L |title=Genomic organization of LPS-specific loci |journal=Curr Top Microbiol Immunol |volume=264 |issue=1 |pages=109–35 |year=2002 |pmid=12014174}}</ref><ref>{{cite journal |author=Patil P, Sonti R |title=Variation suggestive of horizontal gene transfer at a lipopolysaccharide (lps) biosynthetic locus in Xanthomonas oryzae pv. oryzae, the bacterial leaf blight pathogen of rice |journal=BMC Microbiol |volume=4 |issue=1 |pages=40 |year=2004 |pmid=15473911 |doi=10.1186/1471-2180-4-40}}</ref> ==References== {{Reflist|2}} ==See also== * [[Endotoxin]] * [[Mucopolysaccharide]] ==External links== * {{MeshName|Lipopolysaccharides}} [[Category:Membrane-active molecules]] [[Category:Microbiology]] [[de:Lipopolysaccharide]] [[es:Lipopolisacárido]] [[fr:Lipopolysaccharide]] [[gl:Lipopolisacárido]] [[it:Lipopolisaccaride]] [[he:ליפופוליסכריד]] [[ja:リポ多糖]] [[pl:Lipopolisacharyd]] [[pt:Lipopolissacarídeo]] [[fi:Lipopolysakkaridi]] [[sv:Lipopolysackarider]] [[uk:Ліпополісахариди]] [[zh:脂多糖]]