Gene/Protein
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Gene/Protein
Disease
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Target Concepts:
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Query: UMLS:C0036690 (
sepsis
)
59,461
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Endotoxins (lipopolysaccharides, LPS) are the main surface antigens and virulence factors of Gram-negative bacteria involved for example in the development of nosocomial infections and
sepsis
. They consist of three main regions: O-specific polysaccharide, core oligosaccharide, and lipid A. Bacteria modify LPS structure to escape the immune defence, but also to adapt to environmental conditions. LPS's structures are highly diversified in the O-specific polysaccharide region to evade bactericidal factors of immune system, but retain some common epitopes that are potential candidates for therapeutic strategies against bacterial infections. Common occurrence of glycine within the structure of LPS is a known phenomenon and was previously reported for variety of species. Since glycine residue substitutes mainly core oligosaccharide of LPS, especially inner core region, it was also considered as a part of common epitope for broad-reactive antimicrobial antibodies. Herein, we used multiple-stage electrospray ionisation mass spectrometry to identify glycine substitution in core oligosaccharide type characteristic for
Hafnia
alvei LPS, and isolated from five strains of different O-serotypes: 32, PCM 1190, PCM 1192, PCM 1200, and PCM 1209. The location of glycine in core oligosaccharide was determined in detail for LPS 1190 using ESI-MS(n). Three glycoforms were identified, including two mono-glycinylated and one diglycinylated core oligosaccharides.
...
PMID:Occurrence of glycine in the core oligosaccharides of Hafnia alvei lipopolysaccharides--identification of disubstituted glycoform. 2554 Oct 16
Lipopolysaccharide (LPS, endotoxin), the main surface antigen and virulence factor of Gram-negative bacteria, is composed of lipid A, core oligosaccharide, and O-specific polysaccharide (O-PS) regions. Each LPS region is capable of complement activation. We have demonstrated that LPS of
Hafnia
alvei
, an opportunistic human pathogen, reacts strongly with human and murine mannose-binding lectins (MBLs). Moreover, MBL-LPS interactions were detected for the majority of other Gram-negative species investigated.
H. alvei
was used as a model pathogen to investigate the biological consequences of these interactions. The core oligosaccharide region of
H. alvei
LPS was identified as the main target for human and murine MBL, especially l-
glycero
-d-
manno
-heptose (Hep) and
N
-acetyl-d-glucosamine (GlcNAc) residues within the outer core region. MBL-binding motifs of LPS are accessible to MBL on the surface of bacterial cells and LPS aggregates. Generally, the accessibility of outer core structures for interaction with MBL is highest during the lag phase of bacterial growth. The LPS core oligosaccharide-MBL interactions led to complement activation and also induced an anaphylactoid shock in mice. Unlike
Klebsiella pneumoniae
O3 LPS, robust lectin pathway activation of
H. alvei
LPS
in vivo
was mainly the result of outer core recognition by MBL; involvement of the O-PS is not necessary for anaphylactoid shock induction. Our results contribute to a better understanding of MBL-LPS interaction and may support development of therapeutic strategies against
sepsis
based on complement inhibition.
...
PMID:Interaction of Mannose-Binding Lectin With Lipopolysaccharide Outer Core Region and Its Biological Consequences. 3000 19
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