Lipooligosaccharides (LOS) are glycolipids found in the outer membrane of some types of Gram negative bacteria, such as Neisseria spp. and Haemophilus spp. The term is synonymous with the low molecular weight form (see below) of bacterial lipopolysaccharide (LPS; also referred to as endotoxin).[1] LOS plays a central role in maintaining the integrity and functionality of the outer membrane of the Gram negative cell envelope. Lipooligosaccharides play an important role in the pathogenesis of certain bacterial infections because they are capable of acting as immunostimulators and immunomodulators.[1] Furthermore, LOS molecules are responsible for the ability of some bacterial strains to display molecular mimicry and antigenic diversity, aiding in the evasion of host immune defenses and thus contributing to the virulence of these bacterial strains.
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Contents
- 1 Biochemical characteristics
- 2 Molecular mimicry
- 3 Immune system evasion
- 4 Disease manifestations
- 5 See also
- 6 References
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Biochemical characteristics[edit]
Chemically, lipooligosaccharides possess two main structural features: a lipid A-based outer membrane-anchoring moiety, and an oligosaccharide core.[2] The oligosaccharide core is composed of an oligosaccharide inner core, and a short oligosaccharide chain called the outer core which faces the environment. In the case of Neisseria meningitidis, the lipid A portion of the molecule has a symmetrical structure and the inner core is composed of 3-deoxy-D-manno-2-octulosonic acid (KDO) and heptose (Hep) moieties. The outer core oligosaccharide chain varies depending on the bacterial strain. [1] [2] The term lipooligosaccharide is used to refer to the low molecular weight form of bacterial lipopolysaccharides, which can be categorized into two forms: the high molecular weight (Mr, or smooth) form possesses a high molecular weight, repeating polysaccharide O-chain, while the low molecular weight (low-Mr or rough) form, lacks the O-chain but possesses a short oligosaccharide in its place.[1]
Molecular mimicry[edit]
The ability of some bacteria to present molecules on their surface which are chemically identical or similar to the surface molecules of some types of host cells is termed molecular mimicry. This can cause T-cells that recognize pathogen epitopes to cross-react with host epitopes, with an autoimmune-based host response as the result. [3] Portions of the lipooligosaccharides from several bacterial strains have been shown to be chemically similar to human host cell surface molecules. For example, in Neisseria meningitidis L2,3,5,7,9, the terminal tetrasaccharide portion of the oligosaccharide (lacto-N-neotetraose) is the same tetrasaccharide as that found in paragloboside, a precursor for ABH glycolipid antigens found on human erythrocytes.[1] In another example, the terminal trisaccharide portion (lactotriaose) of the oligosaccharide from pathogenic Neisseria spp. LOS is also found in lactoneoseries glycosphingolipids from human cells.[1] Most meningococci from groups B and C, as well as gonococci, have been shown to have this trisaccharide as part of their LOS structure.[1] Other examples of bacterial mimicry of host structures via LPS are found with the bacteria Helicobacter pylori and Campylobacter jejuni, organisms which cause gastrointestinal disease in humans, and Haemophilus ducreyi which causes chancroid. Certain C. jejuni LPS serotypes (attributed to certain tetra- and pentasaccharide moieties of the core oligosaccharide) have also been implicated with Guillain-Barré syndrome and a variant of Guillain-Barré called Miller-Fisher syndrome.[1] The presence of these human cell surface ‘mimics’ may, in addition to acting as a ‘camouflage’ from the immune system, play a role in the abolishment of immune tolerance when infecting hosts with certain human leukocyte antigen (HLA) genotypes, such as HLA-B35.[1]
Immune system evasion[edit]
Normal human blood serum contains anti-LOS antibodies that are bactericidal and patients that have infections caused by serotypically distinct strains possess anti-LOS antibodies that differ in their specificity compared with normal serum.[4] These differences in humoral immune response to different LOS types can be attributed to the structure of the LOS molecule, primarily within the structure of the oligosaccharide portion of the LOS molecule.[4] In Neisseria gonorrhoeae it has been demonstrated that the antigenicity of LOS molecules can change during an infection due to the ability of these bacteria to synthesize more than one type of LOS[4], a characteristic known as phase variation. Additionally, Neisseria gonorrhoeae, as well as Neisseria meningitidis and Haemophilus influenzae,[1] are capable of further modifying their LOS in vitro, for example through sialylation (modification with sialic acid residues), and as a result are able to increase their resistance to complement-mediated killing [4] or even down-regulate complement activation[1] or evade the effects of bactericidal antibodies.[1] Sialylation may also contribute to hindered neutrophil attachment and phagocytosis by immune system cells as well as a reduced oxidative burst.[1] Haemophilus somnus, a pathogen of cattle, has also been shown to display LOS phase variation, a characteristic which may help in the evasion of bovine host immune defenses.[5] Taken together, these observations suggest that variations in bacterial surface molecules such as LOS can help the pathogen evade both the humoral (antibody and complement-mediated) and the cell-mediated (killing by neutrophils, for example) host immune defenses.
Disease manifestations[edit]
Lipid A may cause uncontrolled activation of mammalian immune systems with production of inflammatory mediators that may lead to septic shock.[2] This inflammatory reaction is mediated by Toll-like receptor 4 which is responsible for immune system cell activation.[2] Damage to the endothelial layer of blood vessels caused by these inflammatory mediators can lead to capillary leak syndrome, dilation of blood vessels and a decrease in cardiac function and can lead to septic shock.[6] Pronounced complement activation can also be observed later in the course as the bacteria multiply in the blood.[6] High bacterial proliferation triggering destructive endothelial damage can also lead to disseminated intravascular coagulation (DIC) with loss of function of certain internal organs such as the kidneys, adrenal glands and lungs due to compromised blood supply. The skin can show the effects of vascular damage often coupled with depletion of coagulation factors in the form of petechiae, purpura and ecchymoses. The limbs can also be affected, sometimes with devastating consequences such as the development of gangrene, requiring subsequent amputation.[6] Loss of function of the adrenal glands can cause adrenal insufficiency and additional hemorrhage into the adrenals causes Waterhouse-Friderichsen syndrome, both of which can be life threatening. It has also been reported that gonococcal LOS can cause damage to human fallopian tubes.[4]
See also[edit]
- Endotoxin
- Lipopolysaccharide
References[edit]
- ^ a b c d e f g h i j k l m Moran, Anthony P.; Martina M. Prendergast, Ben J. Appelmelk (1996). "Molecular mimicry of host structures by bacterial lipopolysaccharides and its contribution to disease.". FEMS Immunology and Medical Microbiology 16: 105–115.
- ^ a b c d Kilár, Anikó; Ágnes Dörnyei, Béla Kocsis (2013). "STRUCTURAL CHARACTERIZATION OF BACTERIAL LIPOPOLYSACCHARIDES WITH MASS SPECTROMETRY AND ON- AND OFF-LINE SEPARATION TECHNIQUES". Mass Spectrometry Reviews 32: 90–117.
- ^ Chastain, Emily M. L.; Stephen D. Miller (2012). "Molecular mimicry as an inducing trigger for CNS autoimmune demyelinating disease.". Immunological Reviews 245: 227–238.
- ^ a b c d e Yamasaki, Ryohei; Deborah E. Kerwood, Herman Schneider, Kevin P. Quinn, J. McLeod Griffiss, and Robert E. Mandrell (1994). "The Structure of Lipooligosaccharide Produced by Neisseria gonorrhoeae, Strain 15253, Isolated from a Patient with Disseminated Infection: EVIDENCE FOR A NEW GLYCOSYLATION PATHWAY OF THE GONOCOCCAL LIPOOLIGOSACCHARIDE". The Journal of Biological Chemistry 269 (December 2): 30345–30351.
- ^ HOWARD, MICHAEL D.; ANDREW D. COX, JEFFREY N. WEISER, GERHARDT G. SCHURIG, AND THOMAS J. INZANA (2000). "Antigenic Diversity of Haemophilus somnus Lipooligosaccharide: Phase-Variable Accessibility of the Phosphorylcholine Epitope.". JOURNAL OF CLINICAL MICROBIOLOGY 38 (12): 4412–4419.
- ^ a b c Stephens, David S; Brian Greenwood, Petter Brandtzaeg (2007). "Epidemic meningitis, meningococcaemia, and Neisseria meningitidis.". Lancet 369: 2196–210.
