Found 15 structures.
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1. Compound ID: 8566
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b-D-GlcpNAc3NAcA-(1-4)-+
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-6)-b-D-Glcp-(1-3)-b-D-GalpNAc-(1-3)-a-D-Galp-(1-
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b-D-GlcpNAc-(1-6)-+ |
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Structure type: polymer chemical repeating unit
Compound class: CPS, O-polysaccharide, O-antigen
Contained glycoepitopes: IEDB_130648,IEDB_135813,IEDB_136906,IEDB_137340,IEDB_137472,IEDB_137473,IEDB_140529,IEDB_141794,IEDB_141807,IEDB_142488,IEDB_146664,IEDB_151528,IEDB_151531,IEDB_167069,IEDB_190606,IEDB_983931,SB_192,SB_21,SB_7
The structure is contained in the following publication(s):
- Article ID: 3738
MacLean LL, Perry MB, Chen W, Vinogradov E "The structure of the polysaccharide O-chain of the LPS from Acinetobacter baumannii strain ATCC 17961" -
Carbohydrate Research 344(4) (2009) 474-478
The gram-negative bacterium Acinetobacter baumannii strain ATCC17961 has been used by several laboratories in mouse models of respiratory A. baumannii infection, and a study of the role of its lipopolysaccharide in the pathogenicity is of interest. The structure of the O-deacylated polysaccharide O-chain component of its LPS has been determined by 2D NMR spectroscopy and mass spectrometry methods, and by the structural identification of oligosaccharides obtained by sequential application of the Smith degradation of the O-antigen. The O-chain was determined to be a polymer of a branched pentasaccharide repeating unit composed of 2,3-diacetamido-2,3-dideoxy-d-glucuronic acid, 2-acetamido-2-deoxy-d-glucose, 2-acetamido-2-deoxy-d-galactose, d-glucose, and d-galactose, and has the following structure: (see text).
Lipopolysaccharide, NMR, LPS, structure, polysaccharide, O-antigen, Acinetobacter, Baumannii
NCBI PubMed ID: 19187931Publication DOI: 10.1016/j.carres.2008.12.026Journal NLM ID: 0043535Publisher: Elsevier
Correspondence: E. Vinogradov
Institutions: Institute for Biological Sciences, National Research Council Canada, 100 Sussex Dr., Ottawa, ON, Canada K1A 0R6
Methods: 13C NMR, 1H NMR, GLC-MS, NMR-2D, HF solvolysis, SDS-PAGE, sugar analysis, ESI-MS, Smith degradation, NMR-1D, methanolysis, hydrazinolysis
- Article ID: 4024
Fregolino E, Gargiulo V, Lanzetta R, Parrilli M, Holst O, Castro CD "Identification and structural determination of the capsular polysaccharides from two Acinetobacter baumannii clinical isolates, MG1 and SMAL" -
Carbohydrate Research 346(7) (2011) 973-977
The structures of the capsular polysaccharides (CPSs) of the two clinical isolates Acinetobacter baumannii SMAL and MG1 were elucidated. Hot phenol/water extractions of the dry biomasses, followed by enzymatic digestions and repeated ultracentrifugations led to the isolation of polysaccharides that were negative in Western blot analysis utilizing an anti-lipid A antibody, thus proving that they were not the LPS O-antigens but CPSs. Their structures were established on the basis of NMR spectroscopy and GC-MS analyses. The A. baumannii MG1 CPS consisted of a linear aminopolysaccharide with acyl substitution heterogeneity at the N-4 amino group of QuipN4N: 4)-α-D-GlcpNAc-(1→4)-α-L-GalpNAcA-(1→3)-β-D-QuipNAc4NR-(1→ R=3-hydroxybutyrryl or acetyl. The repeating unit of the CPS produced by strain SMAL is a pentasaccharide, already reported for the O-antigen moiety from A. baumannii strain ATCC 17961: (formula, see text).
Acinetobacter baumannii, capsular polysaccharide, structural analysis, Western blot
NCBI PubMed ID: 21463855Publication DOI: 10.1016/j.carres.2011.03.024Journal NLM ID: 0043535Publisher: Elsevier
Correspondence: decastro@unina.it
Institutions: Division of Structural Biochemistry, Research Center Borstel, Leibniz-Center for Medicine and Biosciences, Borstel, Germany, Università di Napoli Federico II, Dipartimento di Chimica Organica e Biochimica, Complesso Universitario Monte Sant’Angelo, Napoli, Italy
Methods: 13C NMR, 1H NMR, SDS-PAGE, sugar analysis, deacylation, Western blotting, NMR-1D
- Article ID: 4329
Knirel YA "Structure of O-antigens" -
Book: Bacterial lipopolysaccharides: Structure, chemical synthesis, biogenesis and interaction with host cells (2011) Chapter 3, 41-115
The lipopolysaccharide (LPS) is the major constituent of the outer leaflet of the outer membrane of Gram-negative bacteria. Its lipid A moiety is embedded in the membrane and serves as an anchor for the rest of the LPS molecule. The outermost repetitive glycan region of the LPS is linked to the lipid A through a core oligosaccharide (OS), and is designated as the O-specific polysaccharide (O-polysaccharide, OPS) or O-antigen. The O-antigen is the most variable portion of the LPS and provides serological specificity, which is used for bacterial serotyping. The OPS also provides protection to the microorganisms from host defenses such as complement mediated killing and phagocytosis, and is involved in interactions of bacteria with plants and bacteriophages. Studies of the OPSs ranging from the elucidation of their chemical structures and conformations to their biological and physico-chemical properties help improving classification schemes of Gram-negative bacteria. Furthermore, these studies contributed to a better understanding of the mechanisms of pathogenesis of infectious diseases, as well as provided information to develop novel vaccines and diagnostic reagents.
Lipopolysaccharide, synthesis, lipopolysaccharides, structure, Bacterial, host, O-antigen, O antigen, cell, O antigens, O-antigens, chemical, interaction, cells, PDF, chemical synthesis, biogenesis
Publication DOI: 10.1007/978-3-7091-0733-1_3Publisher: Springer
Correspondence: knirel@ioc.ac.ru
Editors: Knirel YA, Valvano MA
Institutions: Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russia
- Article ID: 4748
Arbatsky NP, Shneider MM, Kenyon JJ, Shashkov AS, Popova AV, Miroshnikov KA, Volozhantsev NV, Knirel YA "Structure of the neutral capsular polysaccharide of Acinetobacter baumannii NIPH146 that carries the KL37 capsule gene cluster" -
Carbohydrate Research 413 (2015) 12-15
Capsular polysaccharide (CPS) was isolated from Acinetobacter baumannii NIPH146, and the following structure of branched pentasaccharide repeating unit was established by sugar analyses along with 1D and 2D NMR spectroscopy: In comparison to most other known capsular polysaccharides of A. baumannii, the CPS studied is neutral and lacks any specific monosaccharide component. The synthesis, assembly and export of this structure could be attributed to genes in a novel capsule biosynthesis gene cluster, designated KL37, which was found in the NIPH146 genome. The CPS of A. baumannii NIPH146 shares the α-d-Galp-(1→6)-β-d-Glcp-(1→3)-d-GalpNAc-(1→ trisaccharide fragment with the CPS units of several A. baumannii strains, including ATCC 17978 and LUH 5537 that carry the KL3 and KL22 gene clusters, respectively. KL37 contains two genes for glycosyltransferases that are related to two glycosyltransferase genes present in both KL3 and KL22, and the encoded proteins could be tentatively assigned to linkages between sugars in the CPS repeat.
Acinetobacter baumannii, capsular polysaccharide structure, glycosyltransferase, K locus, KL37 gene cluster
NCBI PubMed ID: 26057991Publication DOI: 10.1016/j.carres.2015.05.003Journal NLM ID: 0043535Publisher: Elsevier
Correspondence: Y.A. Knirel
Institutions: N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russia, State Research Center for Applied Microbiology and Biotechnology, Obolensk, Moscow Region, Russia, M. M. Shemyakin and Y. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia, School of Molecular Bioscience, The University of Sydney, Sydney, Australia, School of Biomedical Sciences, Queensland University of Technology, Brisbane, Australia, Moscow Institute of Physics and Technology, Dolgoprudny, Moscow Region, Russia
Methods: 13C NMR, 1H NMR, NMR-2D, sugar analysis, acid hydrolysis, GLC, NMR-1D, bioinformatic analysis
- Article ID: 4819
Giguere D "Surface polysaccharides from Acinetobacter baumannii: Structures and syntheses" -
Carbohydrate Research 418 (2015) 29-43
The emergence of multidrug-resistance Acinetobacter baumannii requires novel approaches for prevention, treatment and diagnosis. The structures of surface polysaccharides from A. baumannii are valuable tools to understand pathogenesis, virulence and immunogenicity. The synthesis of bacterial mono- or polysaccharides may result in novel probes to become important therapeutic options in the fight against A. baumannii. This report exemplifies the relevance of glycochemistry for the development of new antibiotics.
lipopolysaccharides, capsular polysaccharides, Acinetobacter, Acinetobacter baumannii, polysaccharide synthesis, surface polysaccharides
NCBI PubMed ID: 26531136Publication DOI: 10.1016/j.carres.2015.10.001Journal NLM ID: 0043535Publisher: Elsevier
Correspondence: denis.giguere@chm.ulaval.ca
Institutions: Département de Chimie, Université Laval, Québec City, Québec, Canada G1V 0A6
- Article ID: 5159
Harding CM, Haurat MF, Vinogradov E, Feldman MF "Distinct amino acid residues confer one of three UDP-sugar substrate specificities in Acinetobacter baumannii PglC phosphoglycosyltransferases" -
Glycobiology 28(7) (2018) 522-533
Acinetobacter baumannii is an opportunistic human pathogen with the highest reported rates of multidrug resistance among Gram-negative pathogens. The capsular polysaccharide of A. baumannii is considered one of its most significant virulence factors providing resistance against complemented-mediated killing. Capsule synthesis in A. baumannii is usually initiated by the phosphoglycosyltransferase PglC. PglC transfers a phosphosugar from a nucleotide diphosphate-sugar to a polyprenol phosphate generating a polyprenol diphosphate-linked monosaccharide. Traditionally, PglC was thought to have stringent specificity towards UDP-N-N'-diacetylbacillosamine (UDP-diNAcBac). In this work we demonstrate that A. baumannii PglC has the ability to utilize three different UDP-sugar substrates: UDP-N-acetylglucosamine (UDP-GlcNAc), UDP-N-acetylgalactosamine (UDP-GalNAc) or UDP-diNAcBac. Using phylogenetic analyses, we first demonstrate that A. baumannii PglC orthologs separate into three distinct clades. Moreover, all members within a clade are predicted to have the same preference for one of the three possible sugar substrates. To experimentally determine the substrate specificity of each clade, we utilized in vivo complementation models and NMR analysis. We demonstrate that UDP-diNAcBac is accommodated by all PglC orthologs, but some orthologs evolved to utilize UDP-GlcNAc or UDP-GalNAc in a clade-dependent manner. Furthermore, we show that a single point mutation can modify the sugar specificity of a PglC ortholog specific for UDP-diNAcBac and that introduction of a non-native PglC ortholog into A. baumannii can generate a new capsule serotype. Collectively, these studies begin to explain why A. baumannii strains have such highly diverse glycan repertoires.
serotype, Acinetobacter baumannii, capsular polysaccharide, capsule, PglC, phosphoglycosyltransferase
NCBI PubMed ID: 29668902Publication DOI: 10.1093/glycob/cwy037Journal NLM ID: 9104124Publisher: IRL Press at Oxford University Press
Correspondence: mariofeldman@wustl.edu
Institutions: National Research Council Canada, Human Health Therapeutics, Ottawa, Ontario, Canada K1A 0R6, Department of Molecular Microbiology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA, VaxNewMo LLC, St. Louis, MO 63108, USA
Methods: 13C NMR, SDS-PAGE, Western blotting, genetic methods, cloning, phylogenetic analysis1H NMR
- Article ID: 5204
Qin C, Schumann B, Zou X, Pereira CL, Tian G, Xu J, Seeberger PH, Yin J "Total Synthesis of a Densely Functionalized Plesiomonas shigelloides Serotype 51 Aminoglycoside Trisaccharide Antigen" -
Journal of the American Chemical Society 140(8) (2018) 3120-3127
Plesiomonas shigelloides, a pathogen responsible for frequent outbreaks of severe travelers' diarrhea, causes grave extraintestinal infections. Sepsis and meningitis due to P. shigelloides are associated with a high mortality rate as antibiotic resistance increases and vaccines are not available. Carbohydrate antigens expressed by pathogens are often structurally unique and are targets for developing vaccines and diagnostics. Here, we report a total synthesis of the highly functionalized trisaccharide repeating unit 2 from P. shigelloides serotype 51 from three monosaccharides. A judicious choice of building blocks and reaction conditions allowed for the four amino groups adorning the sugar rings to be installed with two N-acetyl (Ac) groups, rare acetamidino (Am), and d-3-hydroxybutyryl (Hb) groups. The strategy for the differentiation of amino groups in trisaccharide 2 will serve well for the syntheses of other complex glycans.
synthesis, serotype, trisaccharide, vaccine, Plesiomonas shigelloides, total synthesis, carbohydrate chemistry
NCBI PubMed ID: 29377682Publication DOI: 10.1021/jacs.8b00148Journal NLM ID: 7503056Publisher: American Chemical Society
Correspondence: peter.seeberger@mpikg.mpg.de; jianyin@jiangnan.edu.cn
Institutions: Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces , Am Muhlenberg 1, 14476 Potsdam, Germany, Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University , Wuxi, Jiangsu Province 214122, P.R. China
Methods: 13C NMR, 1H NMR, NMR-2D, chemical synthesis, chemical methods, glycosylation
- Article ID: 5791
Knirel YA, Van Calsteren M "Bacterial exopolysaccharides" -
Book: Comprehensive Glycoscience: From Chemistry to Systems Biology. Reference Module in Chemistry, Molecular Sciences and Chemical Engineering (2021) 1-75
Bacterial extracellular polysaccharides are known as a cell-bound capsule, a sheath, or a slime, which is excreted into the environment. They play an important role in virulence of medical bacteria and plant-to-symbiont interaction and are used for serotyping of bacteria and production of vaccines. Some exopolysaccharides have commercial applications in industry, and claims of health benefits have been documented for an increasing number of them. Exopolysaccharides have diverse composition and structure, and some contain sugar and non-sugar components that are found in bacterial carbohydrates only. The present article provides an updated collection of the data on exopolysaccharides of various classes of gram-negative and gram-positive bacteria reported until the end of 2019. When known, biosynthesis pathways of exopolysaccharides are treated in a summary manner. References are made to structure and biosynthesis relatedness between exopolysaccharides of different bacterial taxa as well as between bacterial polysaccharides and mammalian glycosaminoglycans.
polysaccharide structure, Gram-negative bacteria, capsule, Biofilm, polysaccharide biosynthesis, gram-positive bacteria, Monosaccharide composition, Bacterial exopolysaccharide, non-sugar component
Publication DOI: 10.1016/B978-0-12-819475-1.00005-5Publisher: Elsevier
Correspondence: marie-rose.vancalsteren@canada.ca; yknirel@gmail.com
Editors: Barchi J, Kamerling H
Institutions: N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russia, Saint-Hyacinthe Research and Development Centre, Agriculture and Agri-Food Canada, Saint-Hyacinthe, QC, Canada
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2. Compound ID: 9363
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Lau-(1-3)-3HOLau-(1-3)-+ 3HOMyr-(1-2)-+
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3HOMyr-(1-3)-3HOLau-(1-2)-b-D-GlcpN-(1-6)-a-D-GlcpN-(1-P
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P-4)-+ 3HOLau-(1-3)-+ |
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Structure type: oligomer
; 1729.12
Compound class: lipid A
Contained glycoepitopes: IEDB_135394,IEDB_135515,IEDB_141807,IEDB_151531,IEDB_534864
The structure is contained in the following publication(s):
- Article ID: 3985
Arroyo LA, Herrera CM, Fernandez L, Hankins JV, Trent MS, Hancock RE "The pmrCAB operon mediates polymyxin resistance in Acinetobacter baumannii ATCC 17978 and clinical isolates through phosphoethanolamine modification of lipid A" -
Antimicrobial Agents and Chemotherapy 55(8) (2011) 3743-3751
The emergence of multidrug resistance among Acinetobacter baumannii is leading to an increasing dependence on the use of polymyxins as last-hope antibiotics. Here, we utilized genetic and biochemical methods to define the involvement of the pmrCAB operon in polymyxin resistance in this organism. Sequence analysis of 16 polymyxin B-resistant strains, including 6 spontaneous mutants derived from strain ATCC 17978 and 10 clinical isolates from diverse sources, revealed that they had independent mutations in the pmrB gene, encoding a sensor kinase, or in the response regulator PmrA. Knockout of the pmrB gene in two mutants and two clinical isolates led to a decrease in the polymyxin B susceptibility of these strains, which could be restored with the cloned pmrAB genes from the mutants but not from the wild type. Reverse transcription-quantitative PCR (RT-qPCR) analysis also showed a correlation between the expression of pmrC and polymyxin B resistance. Characterization of lipid A species from the mutant strains, by thin-layer chromatography and mass spectrometry, indicated that the addition of phosphoethanolamine to lipid A correlated with resistance. This addition is performed in Salmonella enterica serovar Typhimurium by the product of the pmrC gene, which is a homolog of the pmrC gene from Acinetobacter. Knockout of this gene in the mutant R2 [pmrB(T235I)] reversed resistance as well as phosphoethanolamine modification of lipid A. These results demonstrate that specific alterations in the sequence of the pmrCAB operon are responsible for resistance to polymyxins in A. baumannii.
Acinetobacter baumannii, lipid A, mass spectrometry, phosphoethanolamine, Polymyxin B, pmrCAB
NCBI PubMed ID: 21646482Journal NLM ID: 0315061Correspondence: bob@cmdr.ubc.ca
Institutions: Centre for Microbial Diseases and Immunity Research, 232-2259 Lower Mall Research Station, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada, Section of Molecular Genetics and Microbiology, University of Texas at Austin, Austin, Texas 787122, Department of Molecular Biology and Biochemistry, Georgia Health Sciences University, Augusta, Georgia 30912
Methods: DNA sequencing, TLC, MALDI-TOF MS, genetic methods, biochemical methods
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3. Compound ID: 9364
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Lau-(1-3)-3HOMyr-(1-2)-+
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Lau-(1-3)-3HOLau-(1-3)-+ |
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3HOMyr-(1-3)-3HOLau-(1-2)-b-D-GlcpN-(1-6)-a-D-GlcpN-(1-P
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P-4)-+ 3HOLau-(1-3)-+ |
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Structure type: oligomer
; 1911.29
Compound class: lipid A
Contained glycoepitopes: IEDB_135394,IEDB_135515,IEDB_141807,IEDB_151531,IEDB_534864
The structure is contained in the following publication(s):
- Article ID: 3985
Arroyo LA, Herrera CM, Fernandez L, Hankins JV, Trent MS, Hancock RE "The pmrCAB operon mediates polymyxin resistance in Acinetobacter baumannii ATCC 17978 and clinical isolates through phosphoethanolamine modification of lipid A" -
Antimicrobial Agents and Chemotherapy 55(8) (2011) 3743-3751
The emergence of multidrug resistance among Acinetobacter baumannii is leading to an increasing dependence on the use of polymyxins as last-hope antibiotics. Here, we utilized genetic and biochemical methods to define the involvement of the pmrCAB operon in polymyxin resistance in this organism. Sequence analysis of 16 polymyxin B-resistant strains, including 6 spontaneous mutants derived from strain ATCC 17978 and 10 clinical isolates from diverse sources, revealed that they had independent mutations in the pmrB gene, encoding a sensor kinase, or in the response regulator PmrA. Knockout of the pmrB gene in two mutants and two clinical isolates led to a decrease in the polymyxin B susceptibility of these strains, which could be restored with the cloned pmrAB genes from the mutants but not from the wild type. Reverse transcription-quantitative PCR (RT-qPCR) analysis also showed a correlation between the expression of pmrC and polymyxin B resistance. Characterization of lipid A species from the mutant strains, by thin-layer chromatography and mass spectrometry, indicated that the addition of phosphoethanolamine to lipid A correlated with resistance. This addition is performed in Salmonella enterica serovar Typhimurium by the product of the pmrC gene, which is a homolog of the pmrC gene from Acinetobacter. Knockout of this gene in the mutant R2 [pmrB(T235I)] reversed resistance as well as phosphoethanolamine modification of lipid A. These results demonstrate that specific alterations in the sequence of the pmrCAB operon are responsible for resistance to polymyxins in A. baumannii.
Acinetobacter baumannii, lipid A, mass spectrometry, phosphoethanolamine, Polymyxin B, pmrCAB
NCBI PubMed ID: 21646482Journal NLM ID: 0315061Correspondence: bob@cmdr.ubc.ca
Institutions: Centre for Microbial Diseases and Immunity Research, 232-2259 Lower Mall Research Station, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada, Section of Molecular Genetics and Microbiology, University of Texas at Austin, Austin, Texas 787122, Department of Molecular Biology and Biochemistry, Georgia Health Sciences University, Augusta, Georgia 30912
Methods: DNA sequencing, TLC, MALDI-TOF MS, genetic methods, biochemical methods
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4. Compound ID: 10410
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b-D-GlcpNAc-(1-6)-+
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b-D-GlcpNAc3NAcA4Ac-(1-4)-a-D-Galp-(1-6)-b-D-Glcp-(1-3)-b-D-GalpNAc-(1-3)-Ser-(?-?)-Glu-(?-?)-Ala |
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Structure type: oligomer
Trivial name: O-glycan
Contained glycoepitopes: IEDB_130648,IEDB_135813,IEDB_136906,IEDB_137340,IEDB_137472,IEDB_137473,IEDB_140529,IEDB_141794,IEDB_141807,IEDB_142488,IEDB_146664,IEDB_150900,IEDB_151528,IEDB_151531,IEDB_167069,IEDB_190606,IEDB_983931,SB_192,SB_7
The structure is contained in the following publication(s):
- Article ID: 4320
Iwashkiw JA, Seper A, Weber BS, Scott NE, Vinogradov E, Stratilo C, Reiz B, Cordwell SJ, Whittal R, Schild S, Feldman MF "Identification of a General O-linked Protein Glycosylation System in Acinetobacter baumannii and Its Role in Virulence and Biofilm Formation" -
PLoS Pathogens 8(6) (2012) e1002758
Acinetobacter baumannii is an emerging cause of nosocomial infections. The isolation of strains resistant to multiple antibiotics is increasing at alarming rates. Although A. baumannii is considered as one of the more threatening 'superbugs' for our healthcare system, little is known about the factors contributing to its pathogenesis. In this work we show that A. baumannii ATCC 17978 possesses an O-glycosylation system responsible for the glycosylation of multiple proteins. 2D-DIGE and mass spectrometry methods identified seven A. baumannii glycoproteins, of yet unknown function. The glycan structure was determined using a combination of MS and NMR techniques and consists of a branched pentasaccharide containing N-acetylgalactosamine, glucose, galactose, N-acetylglucosamine, and a derivative of glucuronic acid. A glycosylation deficient strain was generated by homologous recombination. This strain did not show any growth defects, but exhibited a severely diminished capacity to generate biofilms. Disruption of the glycosylation machinery also resulted in reduced virulence in two infection models, the amoebae Dictyostelium discoideum and the larvae of the insect Galleria mellonella, and reduced in vivo fitness in a mouse model of peritoneal sepsis. Despite A. baumannii genome plasticity, the O-glycosylation machinery appears to be present in all clinical isolates tested as well as in all of the genomes sequenced. This suggests the existence of a strong evolutionary pressure to retain this system. These results together indicate that O-glycosylation in A. baumannii is required for full virulence and therefore represents a novel target for the development of new antibiotics.
virulence, Acinetobacter baumannii, Biofilm, O-glycosylation
NCBI PubMed ID: 22685409Publication DOI: 10.1371/journal.ppat.1002758Journal NLM ID: 101238921Publisher: San Francisco, CA: Public Library of Science
Correspondence: mfeldman@ualberta.ca
Institutions: Alberta Glycomics Centre, Department of Biological Sciences, University of Alberta, Edmonton, AB, Canada
Methods: 13C NMR, 1H NMR, NMR-2D, SDS-PAGE, Western blotting, MALDI-TOF MS, composition analysis, genetic methods
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5. Compound ID: 11251
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b-D-GlcpNAc-(1-6)-+
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b-D-GlcpNAc3NAcA4Ac-(1-4)-a-D-Galp-(1-6)-b-D-Glcp-(1-3)-b-D-GalpNAc-(1--/peptide/ |
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Structure type: oligomer
Aglycon: peptide
Compound class: O-glycan
Contained glycoepitopes: IEDB_130648,IEDB_135813,IEDB_136906,IEDB_137340,IEDB_137472,IEDB_137473,IEDB_140529,IEDB_141794,IEDB_141807,IEDB_142488,IEDB_146664,IEDB_151528,IEDB_151531,IEDB_167069,IEDB_190606,IEDB_983931,SB_192,SB_7
The structure is contained in the following publication(s):
- Article ID: 4537
Iwashkiw JA, Vozza NF, Kinsella RL, Feldman MF "Pour some sugar on it: the expanding world of bacterial protein O-linked glycosylation" -
Molecular Microbiology 89(1) (2013) 14-28
Protein glycosylation was once considered as an eccentricity of a few bacteria. However in the recent years multiple O-glycosylation mechanisms have been identified in bacterial species from the most diverse genera, including various important human pathogens. This review focuses on summarizing the structural diversity, the various pathways and the physiological roles of this post-translational protein modification. We propose a classification of O-glycosylation based on the requirement of an oligosaccharyltransferase (OTase). OTase-dependent glycosylation utilizes an oligosaccharide synthesized on a lipid carrier that is transferred to proteins en bloc by an OTase. Multiple proteins, including the pilins, are glycosylated using this mechanism. OTase-independent glycosylation refers to the pathway in which glycosyltransferases sequentially add monosaccharides onto the target proteins. This pathway is employed for glycosylation of flagella and autotransporters. Both systems play key roles in pathogenesis. Exploiting glycosylation machineries it is now possible to generate glycoconjugates made of different proteins attached to polysaccharides derived from LPS or capsule biosynthesis. These recombinant glycoproteins can be exploited for vaccines and diagnostics of bacterial infections. Furthermore, O-glycosylation systems are promising targets for antibiotic development. Technological advances in MS and NMR will facilitate the discovery of novel glycosylation systems. Likely, the O-glycosylation pathways we currently know constitute just the tip of the iceberg of a still largely uncharacterized bacterial glycosylation world.
biosynthesis, glycoconjugates, bacteria, glycosyltransferases, capsule, glycoproteins, flagella, Glycomics, O-glycosylation
NCBI PubMed ID: 23679002Publication DOI: 10.1111/mmi.12265Journal NLM ID: 8712028Publisher: Blackwell Publishing
Correspondence: mfeldman@ualberta.ca
Institutions: Alberta Glycomics Centre, Department of Biological Sciences, University of Alberta, Edmonton, AB, Canada
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6. Compound ID: 11322
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b-D-GlcpNAc3NAcA4Ac-(1-4)-+
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-3)-a-D-Galp-(1-6)-b-D-Glcp-(1-3)-b-D-GalpNAc-(1-
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b-D-GlcpNAc-(1-6)-+ |
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Structure type: polymer chemical repeating unit
Trivial name: O-glycan
Compound class: CPS
Contained glycoepitopes: IEDB_130648,IEDB_135813,IEDB_136906,IEDB_137340,IEDB_137472,IEDB_137473,IEDB_140529,IEDB_141794,IEDB_141807,IEDB_142488,IEDB_146664,IEDB_151528,IEDB_151531,IEDB_167069,IEDB_190606,IEDB_983931,SB_192,SB_21,SB_7
The structure is contained in the following publication(s):
- Article ID: 4562
Lees-Miller RG, Iwashkiw JA, Scott NE, Seper A, Vinogradov E, Schild S, Feldman MF "A common pathway for O-linked protein-glycosylation and synthesis of capsule in Acinetobacter baumannii" -
Molecular Microbiology 89(5) (2013) 816-830
Multi-drug resistant strains of Acinetobacter baumannii are increasingly being isolated in hospitals worldwide. Among the virulence factors identified in this bacterium there is a general O-glycosylation system that appears to be important for biofilm formation and virulence, and the capsular polysaccharide, which is essential for resistance to complement killing. In this work, we identified a locus that is responsible for the synthesis of the O-pentasaccharide found on the glycoproteins. Besides the enzymes required for the assembly of the glycan, additional proteins typically involved in polymerization and transport of capsule were identified within or adjacently to the locus. Mutagenesis of PglC, the initiating glycosyltransferase prevented the synthesis of both glycoproteins and capsule, resulting in abnormal biofilm structures and attenuated virulence in mice. These results, together with the structural analysis of A. baumannii 17978 capsular polysaccharide via NMR, demonstrated that the pentasaccharides that decorate the glycoproteins are also the building blocks for capsule biosynthesis. Two linked subunits, but not longer glycan chains, were detected on proteins via MS. The discovery of a bifurcated pathway for O-glycosylation and capsule synthesis not only provides insight into the biology of A. baumannii but also identifies potential novel candidates for intervention against this emerging pathogen.
Acinetobacter baumannii, capsular polysaccharide, capsule biosynthesis, genetic locus, O-pentasaccharide
NCBI PubMed ID: 23782391Publication DOI: 10.1111/mmi.12300Journal NLM ID: 8712028Publisher: Blackwell Publishing
Correspondence: mfeldman@ualberta.ca
Institutions: Alberta Glycomics Centre, Department of Biological Sciences, University of Alberta, Edmonton, AB, Canada
Methods: 13C NMR, 1H NMR, NMR-2D, SDS-PAGE, DNA techniques, Western blotting, biological assays, microscopy, CID-MS, HILIC-MS
- Article ID: 4819
Giguere D "Surface polysaccharides from Acinetobacter baumannii: Structures and syntheses" -
Carbohydrate Research 418 (2015) 29-43
The emergence of multidrug-resistance Acinetobacter baumannii requires novel approaches for prevention, treatment and diagnosis. The structures of surface polysaccharides from A. baumannii are valuable tools to understand pathogenesis, virulence and immunogenicity. The synthesis of bacterial mono- or polysaccharides may result in novel probes to become important therapeutic options in the fight against A. baumannii. This report exemplifies the relevance of glycochemistry for the development of new antibiotics.
lipopolysaccharides, capsular polysaccharides, Acinetobacter, Acinetobacter baumannii, polysaccharide synthesis, surface polysaccharides
NCBI PubMed ID: 26531136Publication DOI: 10.1016/j.carres.2015.10.001Journal NLM ID: 0043535Publisher: Elsevier
Correspondence: denis.giguere@chm.ulaval.ca
Institutions: Département de Chimie, Université Laval, Québec City, Québec, Canada G1V 0A6
- Article ID: 5056
Yang FL, Lou TC, Kuo SC, Wu WL, Chern J, Lee YT, Chen ST, Zou W, Lin NT, Wu SH "A medically relevant capsular polysaccharide in Acinetobacter baumannii is a potential vaccine candidate" -
Vaccine 35(10) (2017) 1440-1447
Concerns of Acinetobacter baumannii infection have increased due to the emergence of multi-drug resistance. In the present study, we determined the capsular polysaccharide (CPS) structure of A. baumannii SK44, a clinical isolate from Taiwan, to consist of pentasaccharide repeats. We found that CPS-induced antibody provided 55% protection against challenge in an animal model. The CPS-specific antibody reacted with the surface components of about 62% clinical isolates (342/554 strains) from cross-sectional and longitudinal studies by dot-immunoassay. Pulsed-field gel electrophoresis of positive strains showed the antibody covered different clonalites of A. baumannii clinical isolates. Meanwhile, using the CPS antibody as a probe, we found a number of outer membrane proteins bound to the antibody, including OmpA/motB, TonB-dependent receptor, and Omp38, indicating their association with CPS. These results might lead to the use of the capsular polysaccharide as a vaccine to prevent A. baumannii infection.
Acinetobacter baumannii, capsular polysaccharide, Clinic population distribution, Passive immunity
NCBI PubMed ID: 28190743Publication DOI: 10.1016/j.vaccine.2017.01.060Journal NLM ID: 8406899Publisher: Elsevier
Correspondence: shwu@gate.sinica.edu.tw
Institutions: Institute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan, National Health Research Institutes, Miaoli County 35053, Taiwan, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan, Department of Emergency Medicine, Taipei Veterans General Hospital, Taipei 112, Taiwan, Human Health Therapeutics, National Research Council of Canada, 100 Sussex Drive, Ottawa, Ontario K1A0R, Canada, Institute of Microbiology, Tzu Chi University, Hualien 907, Taiwan
Methods: 13C NMR, 1H NMR, methylation, NMR-2D, GC-MS, sugar analysis, acid hydrolysis, MS/MS, serological methods, enzymatic digestion, statistical analysis, SEC, immunization, conjugation, pulsed-field gel electrophoresis (PFGE)
- Article ID: 5500
Singh JK, Adams FG, Brown MH "Diversity and Function of Capsular Polysaccharide in Acinetobacter baumannii" -
Frontiers in Microbiology 9 (2019) 3301
The Gram-negative opportunistic bacterium Acinetobacter baumannii is a significant cause of hospital-borne infections worldwide. Alarmingly, the rapid development of antimicrobial resistance coupled with the remarkable ability of isolates to persist on surfaces for extended periods of time has led to infiltration of A. baumannii into our healthcare environments. A major virulence determinant of A. baumannii is the presence of a capsule that surrounds the bacterial surface. This capsule is comprised of tightly packed repeating polysaccharide units which forms a barrier around the bacterial cell wall, providing protection from environmental pressures including desiccation and disinfection regimes as well as host immune responses such as serum complement. Additionally, capsule has been shown to confer resistance to a range of clinically relevant antimicrobial compounds. Distressingly, treatment options for A. baumannii infections are becoming increasingly limited, and the urgency to develop effective infection control strategies and therapies to combat infections is apparent. An increased understanding of the contribution of capsule to the pathobiology of A. baumannii is required to determine its feasibility as a target for new strategies to combat drug resistant infections. Significant variation in capsular polysaccharide structures between A. baumannii isolates has been identified, with over 100 distinct capsule types, incorporating a vast variety of sugars. This review examines the studies undertaken to elucidate capsule diversity and advance our understanding of the role of capsule in A. baumannii pathogenesis.
polysaccharide, Acinetobacter, Acinetobacter baumannii, capsule, virulence factor, persistence
NCBI PubMed ID: 30687280Publication DOI: 10.3389/fmicb.2018.03301Journal NLM ID: 101548977Publisher: Lausanne: Frontiers Research Foundation
Correspondence: Melissa H. Brown
Institutions: College of Science and Engineering, Flinders University, Bedford Park, SA, Australia.College of Science and Engineering, Flinders University, Bedford Park, SA, Australia
- Article ID: 5791
Knirel YA, Van Calsteren M "Bacterial exopolysaccharides" -
Book: Comprehensive Glycoscience: From Chemistry to Systems Biology. Reference Module in Chemistry, Molecular Sciences and Chemical Engineering (2021) 1-75
Bacterial extracellular polysaccharides are known as a cell-bound capsule, a sheath, or a slime, which is excreted into the environment. They play an important role in virulence of medical bacteria and plant-to-symbiont interaction and are used for serotyping of bacteria and production of vaccines. Some exopolysaccharides have commercial applications in industry, and claims of health benefits have been documented for an increasing number of them. Exopolysaccharides have diverse composition and structure, and some contain sugar and non-sugar components that are found in bacterial carbohydrates only. The present article provides an updated collection of the data on exopolysaccharides of various classes of gram-negative and gram-positive bacteria reported until the end of 2019. When known, biosynthesis pathways of exopolysaccharides are treated in a summary manner. References are made to structure and biosynthesis relatedness between exopolysaccharides of different bacterial taxa as well as between bacterial polysaccharides and mammalian glycosaminoglycans.
polysaccharide structure, Gram-negative bacteria, capsule, Biofilm, polysaccharide biosynthesis, gram-positive bacteria, Monosaccharide composition, Bacterial exopolysaccharide, non-sugar component
Publication DOI: 10.1016/B978-0-12-819475-1.00005-5Publisher: Elsevier
Correspondence: marie-rose.vancalsteren@canada.ca; yknirel@gmail.com
Editors: Barchi J, Kamerling H
Institutions: N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russia, Saint-Hyacinthe Research and Development Centre, Agriculture and Agri-Food Canada, Saint-Hyacinthe, QC, Canada
- Article ID: 6148
Talyansky Y, Nielsen TB, Yan J, Carlino-Macdonald U, Di Venanzio G, Chakravorty S, Ulhag A, Russo TA, Vinogradov E, Luna B, Wright MS, Adams MD, Spellberg B "Capsule carbohydrate structure determines virulence in Acinetobacter baumannii" -
PLoS Pathogens 17(2) (2021) e1009291
Acinetobacter baumannii is a highly antibiotic-resistant bacterial pathogen for which novel therapeutic approaches are needed. Unfortunately, the drivers of virulence in A. baumannii remain uncertain. By comparing genomes among a panel of A. baumannii strains we identified a specific gene variation in the capsule locus that correlated with altered virulence. While less virulent strains possessed the intact gene gtr6, a hypervirulent clinical isolate contained a spontaneous transposon insertion in the same gene, resulting in the loss of a branchpoint in capsular carbohydrate structure. By constructing isogenic gtr6 mutants, we confirmed that gtr6-disrupted strains were protected from phagocytosis in vitro and displayed higher bacterial burden and lethality in vivo. Gtr6+ strains were phagocytized more readily and caused lower bacterial burden and no clinical illness in vivo. We found that the CR3 receptor mediated phagocytosis of gtr6+, but not gtr6-, strains in a complement-dependent manner. Furthermore, hypovirulent gtr6+ strains demonstrated increased virulence in vivo when CR3 function was abrogated. In summary, loss-of-function in a single capsule assembly gene dramatically altered virulence by inhibiting complement deposition and recognition by phagocytes across multiple A. baumannii strains. Thus, capsular structure can determine virulence among A. baumannii strains by altering bacterial interactions with host complement-mediated opsonophagocytosis.
virulence, Acinetobacter baumannii, capsule, carbohydrate structure
NCBI PubMed ID: 33529209Publication DOI: 10.1371/journal.ppat.1009291Journal NLM ID: 101238921Publisher: San Francisco, CA: Public Library of Science
Correspondence: Brad Spellberg
Institutions: Department of Molecular Microbiology & Immunology, University of Southern California, Los Angeles, California, United States of America, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois, United States of America, Division of Infectious Diseases, Department of Medicine, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Veterans Administration, Buffalo, New York, United States of America, Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, United States of America, National Research Council Canada, Human Health Therapeutics Centre, Ottawa, Canada, Rady Children's Institute for Genomic Medicine, San Diego, California, United States of America, The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut, United States of America, LAC+USC Medical Center, Los Angeles, California, United States of America
Methods: PCR, genetic methods, RNA sequencing, flow cytometry, phagocytosis assay, mutant generation, genome BLAST analysis
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7. Compound ID: 12167
|
Lau-(1-3)-R-3HOMyr-(1-2)-+
|
Lau-(1-3)-R-3HOLau-(1-3)-+ |
| |
R-3HOLau-(1-3)-R-3HOMyr-(1-2)-b-D-GlcpN-(1-6)-a-D-GlcpN-(1-P
| |
P-4)-+ |
|
R-3HOLau-(1-3)-+ |
Show graphically |
Structure type: oligomer
Compound class: lipid A
Contained glycoepitopes: IEDB_135394,IEDB_135515,IEDB_141807,IEDB_151531,IEDB_534864
The structure is contained in the following publication(s):
- Article ID: 4837
Boll JM, Tucker AT, Klein DR, Beltran AM, Brodbelt JS, Davies BW, Trent MS "Reinforcing Lipid A Acylation on the Cell Surface of Acinetobacter baumannii Promotes Cationic Antimicrobial Peptide Resistance and Desiccation Survival" -
mBio 6(3) (2015) e00478-15
Acinetobacter baumannii is an emerging Gram-negative pathogen found in hospitals and intensive care units. In order to persist in hospital environments, A. baumannii withstands desiccative conditions and can rapidly develop multidrug resistance to conventional antibiotics. Cationic antimicrobial peptides (CAMPs) have served as therapeutic alternatives because they target the conserved lipid A component of the Gram-negative outer membrane to lyse the bacterial cell. However, many Gram-negative pathogenic bacteria, including A. baumannii, fortify their outer membrane with hepta-acylated lipid A to protect the cell from CAMP-dependent cell lysis. Whereas in Escherichia coli and Salmonella, increased production of the outer membrane acyltransferase PagP results in formation of protective hepta-acylated lipid A, which reinforces the lipopolysaccharide portion of the outer membrane barrier, A. baumannii does not carry a gene that encodes a PagP homolog. Instead, A. baumannii has evolved a PagP-independent mechanism to synthesize protective hepta-acylated lipid A. Taking advantage of a recently adapted A. baumannii genetic recombineering system, we characterized two putative acyltransferases in A. baumannii designated LpxLAb (A. baumannii LpxL) and LpxMAb (A. baumannii LpxM), which transfer one and two lauroyl (C12:0) acyl chains, respectively, during lipid A biosynthesis. Hepta-acylation of A. baumannii lipid A promoted resistance to vertebrate and polymyxin CAMPs, which are prescribed as last-resort treatment options. Intriguingly, our analysis also showed that LpxMAb-dependent acylation of lipid A is essential for A. baumannii desiccation survival, a key resistance mechanism for survival in hospital environments. Compounds that inhibit LpxMAb-dependent hepta-acylation of lipid A could act synergistically with CAMPs to provide innovative transmission prevention strategies and treat multidrug-resistant infections. IMPORTANCE: Acinetobacter baumannii infections can be life threatening, and disease can progress in a variety of host tissues. Current antibiotic regimen and disinfectant strategies have failed to limit nosocomial A. baumannii infections. Instead, the rate of A. baumannii infection among health care communities has skyrocketed due to the bacterium's adaptability. Its aptitude for survival over extended periods on inanimate objects, such as catheters, respirators, and surfaces in intensive care units, or on the hands of health care workers and its ability to rapidly develop antibiotic resistance make A. baumannii a threat to health care communities. Emergence of multidrug- and extremely drug-resistant A. baumannii illustrates the ineffectiveness of current prevention and treatment options. Our analysis to understand how A. baumannii resists cationic antimicrobial peptide (CAMP)-mediated and desiccative killing revealed two lipid A acyltransferases that produce protective hepta-acylated lipid A. Our work suggests that inhibiting lipid A biosynthesis by targeting the acyltransferase LpxMAb (A. baumannii LpxM) could provide a novel target to combat this pathogen.
Escherichia coli, Acinetobacter baumannii, lipid A, acylation, acyltransferases
Publication DOI: 10.1128/mBio.00478-15Journal NLM ID: 101519231Publisher: Washington, DC: American Society for Microbiology
Correspondence: strent@uga.edu
Institutions: Department of Molecular Biosciences, University of Texas at Austin, Austin, Texas, USA, Department of Chemistry, University of Texas at Austin, Austin, Texas, USA, Department of Infectious Diseases, University of Georgia, College of Veterinary Medicine, Athens, Georgia, USA
Methods: TLC, MALDI-TOF MS, genetic methods, MALDI-TOF/TOF MS, bactericidal assays, TLR-4 signaling assays
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8. Compound ID: 13156
|
R-3HOLau-(1-3)-+
|
R-3HOLau-(1-3)-R-3HOMyr-(1-2)-+ /Variants 0/-+ |
| | |
EtN-(1-0)-?%P---P--4)-b-D-GlcpN-(1-6)-a-D-GlcpN
| |
Lau-(1-3)-R-3HOLau-(1-3)-+ |
|
Lau-(1-3)-R-3HOMyr-(1-2)-+
/Variants 0/ is:
?%a-D-GalpN-(1--P--1)--
OR (exclusively)
EtN-(1-0)-?%P---P--1)- |
Show graphically |
Structure type: oligomer
Compound class: lipid A
Contained glycoepitopes: IEDB_120354,IEDB_123890,IEDB_137473,IEDB_141807,IEDB_151531,IEDB_534864
The structure is contained in the following publication(s):
- Article ID: 5202
Powers MJ, Trent MS "Expanding the paradigm for the outer membrane: Acinetobacter baumannii in the absence of endotoxin" -
Molecular Microbiology 107(1) (2018) 47-56
Asymmetry in the outer membrane has long defined the cell envelope of Gram-negative bacteria. This asymmetry, with lipopolysaccharide (LPS) or lipooligosaccharide (LOS) exclusively in the outer leaflet of the membrane, establishes an impermeable barrier that protects the cell from a number of stressors in the environment. Work done over the past 5 years has shown that Acinetobacter baumannii has the remarkable capability to survive with inactivated production of lipid A biosynthesis and the absence of LOS in its outer membrane. The implications of LOS-deficient A. baumannii are far-reaching - from impacts on cell envelope biogenesis and maintenance, bacterial physiology, antibiotic resistance and virulence. This review examines recent work that has contributed to our understanding of LOS-deficiency and compares it to studies done on Neisseria meningitidis and Moraxella catarrhalis; the two other organisms with this capability.
Lipopolysaccharide, Lipooligosaccharide, Acinetobacter baumannii, lipid A, Gram-negative bacteria, barrier, bacterial outer membrane proteins
NCBI PubMed ID: 29114953Publication DOI: 10.1111/mmi.13872Journal NLM ID: 8712028Publisher: Blackwell Publishing
Correspondence: strent@uga.edu
Institutions: Department of Microbiology, University of Georgia, Athens, GA, USA, Department of Infectious Diseases, University of Georgia, 510 DW Brooks Drive, Athens, GA 30602, USA
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9. Compound ID: 15717
|
R-3HOMyr-(1-2)-+
|
P-4)-+ |
| |
R-3HOMyr-(1-2)-+ | |
| | |
a-Kdop-(2-5)-+ | | |
| | | |
a-Kdop-(2-4)-a-Kdop-(2-6)-b-D-GlcpN-(1-6)-a-D-GlcpN-(1-P
| |
R-3HOLau-(1-3)-+ |
|
R-3HOLau-(1-3)-+ |
Show graphically |
Structure type: oligomer
Compound class: LOS, lipid A
Contained glycoepitopes: IEDB_130650,IEDB_130659,IEDB_135394,IEDB_135515,IEDB_141807,IEDB_150908,IEDB_151531
The structure is contained in the following publication(s):
- Article ID: 6068
Herrera CM, Voss BJ, Trent MS "Homeoviscous Adaptation of the Acinetobacter baumannii Outer Membrane: Alteration of Lipooligosaccharide Structure during Cold Stress" -
mBio 12(4) (2021) e0129521
To maintain optimal membrane dynamics, cells from all domains of life must acclimate to various environmental signals in a process referred to as homeoviscous adaptation. Alteration of the lipid composition is critical for maintaining membrane fluidity, permeability of the lipid bilayer, and protein function under diverse conditions. It is well documented, for example, that glycerophospholipid content varies substantially in both Gram-negative and Gram-positive bacteria with changes in growth temperature. However, in the case of Gram-negative bacteria, far less is known concerning structural changes in lipopolysaccharide (LPS) or lipooligosaccharide (LOS) during temperature shifts. LPS/LOS is anchored at the cell surface by the highly conserved lipid A domain and localized in the outer leaflet of the outer membrane. Here, we identified a novel acyltransferase, termed LpxS, involved in the synthesis of the lipid A domain of Acinetobacter baumannii. A. baumannii is a significant, multidrug-resistant, opportunistic pathogen that is particularly difficult to clear from health care settings because of its ability to survive under diverse conditions. LpxS transfers an octanoate (C8:0) fatty acid, the shortest known secondary acyl chain reported to date, replacing a C12:0 fatty acid at the 2' position of lipid A. Expression of LpxS was highly upregulated under cold conditions and likely increases membrane fluidity. Furthermore, incorporation of a C8:0 acyl chain under cold conditions increased the effectiveness of the outer membrane permeability barrier. LpxS orthologs are found in several Acinetobacter species and may represent a common mechanism for adaptation to cold temperatures in these organisms. IMPORTANCE To maintain cellular fitness, the composition of biological membranes must change in response to shifts in temperature or other stresses. This process, known as homeoviscous adaptation, allows for maintenance of optimal fluidity and membrane permeability. Here, we describe an enzyme that alters the fatty acid content of A. baumannii LOS, a major structural feature and key component of the bacterial outer membrane. Although much is known regarding how glycerophospholipids are altered during temperature shifts, our understanding of LOS or LPS alterations under these conditions is lacking. Our work identifies a cold adaptation mechanism in A. baumannii, a highly adaptable and multidrug-resistant pathogen.
Lipopolysaccharide, Lipooligosaccharide, Acinetobacter, Acinetobacter baumannii, lipid A, cell envelope, outer membrane, acylation, acyltransferase, cold shock
NCBI PubMed ID: 34425709Publication DOI: 10.1128/mBio.01295-21Journal NLM ID: 101519231Publisher: Washington, DC: American Society for Microbiology
Correspondence: M. Stephen Trent
Institutions: Department of Infectious Diseases, College of Veterinary Medicine, University of Georgiagrid.213876.9, Athens, Georgia, USA, Department of Microbiology, College of Art and Sciences, University of Georgiagrid.213876.9, Athens, Georgia, USA
Methods: PCR, DNA techniques, TLC, MALDI-TOF MS, radiolabeling, extraction, genome analysis, MIC determination
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10. Compound ID: 15718
|
Lau-(1-3)-R-3HOMyr-(1-2)-+
|
P-4)-+ |
| |
LIP-(1-3)-R-3HOMyr-(1-2)-+ | |
| | |
a-Kdop-(2-5)-+ | | |
| | | |
a-Kdop-(2-4)-a-Kdop-(2-6)-b-D-GlcpN-(1-6)-a-D-GlcpN-(1-P
| |
R-3HOLau-(1-3)-+ |
|
R-3HOLau-(1-3)-+ |
Show graphically |
Structure type: oligomer
Compound class: LOS, lipid A
Contained glycoepitopes: IEDB_130650,IEDB_130659,IEDB_135394,IEDB_135515,IEDB_141807,IEDB_150908,IEDB_151531,IEDB_534864
The structure is contained in the following publication(s):
- Article ID: 6068
Herrera CM, Voss BJ, Trent MS "Homeoviscous Adaptation of the Acinetobacter baumannii Outer Membrane: Alteration of Lipooligosaccharide Structure during Cold Stress" -
mBio 12(4) (2021) e0129521
To maintain optimal membrane dynamics, cells from all domains of life must acclimate to various environmental signals in a process referred to as homeoviscous adaptation. Alteration of the lipid composition is critical for maintaining membrane fluidity, permeability of the lipid bilayer, and protein function under diverse conditions. It is well documented, for example, that glycerophospholipid content varies substantially in both Gram-negative and Gram-positive bacteria with changes in growth temperature. However, in the case of Gram-negative bacteria, far less is known concerning structural changes in lipopolysaccharide (LPS) or lipooligosaccharide (LOS) during temperature shifts. LPS/LOS is anchored at the cell surface by the highly conserved lipid A domain and localized in the outer leaflet of the outer membrane. Here, we identified a novel acyltransferase, termed LpxS, involved in the synthesis of the lipid A domain of Acinetobacter baumannii. A. baumannii is a significant, multidrug-resistant, opportunistic pathogen that is particularly difficult to clear from health care settings because of its ability to survive under diverse conditions. LpxS transfers an octanoate (C8:0) fatty acid, the shortest known secondary acyl chain reported to date, replacing a C12:0 fatty acid at the 2' position of lipid A. Expression of LpxS was highly upregulated under cold conditions and likely increases membrane fluidity. Furthermore, incorporation of a C8:0 acyl chain under cold conditions increased the effectiveness of the outer membrane permeability barrier. LpxS orthologs are found in several Acinetobacter species and may represent a common mechanism for adaptation to cold temperatures in these organisms. IMPORTANCE To maintain cellular fitness, the composition of biological membranes must change in response to shifts in temperature or other stresses. This process, known as homeoviscous adaptation, allows for maintenance of optimal fluidity and membrane permeability. Here, we describe an enzyme that alters the fatty acid content of A. baumannii LOS, a major structural feature and key component of the bacterial outer membrane. Although much is known regarding how glycerophospholipids are altered during temperature shifts, our understanding of LOS or LPS alterations under these conditions is lacking. Our work identifies a cold adaptation mechanism in A. baumannii, a highly adaptable and multidrug-resistant pathogen.
Lipopolysaccharide, Lipooligosaccharide, Acinetobacter, Acinetobacter baumannii, lipid A, cell envelope, outer membrane, acylation, acyltransferase, cold shock
NCBI PubMed ID: 34425709Publication DOI: 10.1128/mBio.01295-21Journal NLM ID: 101519231Publisher: Washington, DC: American Society for Microbiology
Correspondence: M. Stephen Trent
Institutions: Department of Infectious Diseases, College of Veterinary Medicine, University of Georgiagrid.213876.9, Athens, Georgia, USA, Department of Microbiology, College of Art and Sciences, University of Georgiagrid.213876.9, Athens, Georgia, USA
Methods: PCR, DNA techniques, TLC, MALDI-TOF MS, radiolabeling, extraction, genome analysis, MIC determination
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11. Compound ID: 15719
|
Lau-(1-3)-R-3HOMyr-(1-2)-+
|
P-4)-+ |
| |
LIP-(1-3)-R-3HOMyr-(1-2)-+ | |
| | |
a-Kdop-(2-5)-+ | | |
| | | |
a-Kdop-(2-4)-a-Kdop-(2-6)-b-D-GlcpN-(1-6)-a-D-GlcpN-(1-P
| |
Lau-(1-3)-R-3HOLau-(1-3)-+ |
|
R-3HOLau-(1-3)-+ |
Show graphically |
Structure type: oligomer
Compound class: LOS, lipid A
Contained glycoepitopes: IEDB_130650,IEDB_130659,IEDB_135394,IEDB_135515,IEDB_141807,IEDB_150908,IEDB_151531,IEDB_534864
The structure is contained in the following publication(s):
- Article ID: 6068
Herrera CM, Voss BJ, Trent MS "Homeoviscous Adaptation of the Acinetobacter baumannii Outer Membrane: Alteration of Lipooligosaccharide Structure during Cold Stress" -
mBio 12(4) (2021) e0129521
To maintain optimal membrane dynamics, cells from all domains of life must acclimate to various environmental signals in a process referred to as homeoviscous adaptation. Alteration of the lipid composition is critical for maintaining membrane fluidity, permeability of the lipid bilayer, and protein function under diverse conditions. It is well documented, for example, that glycerophospholipid content varies substantially in both Gram-negative and Gram-positive bacteria with changes in growth temperature. However, in the case of Gram-negative bacteria, far less is known concerning structural changes in lipopolysaccharide (LPS) or lipooligosaccharide (LOS) during temperature shifts. LPS/LOS is anchored at the cell surface by the highly conserved lipid A domain and localized in the outer leaflet of the outer membrane. Here, we identified a novel acyltransferase, termed LpxS, involved in the synthesis of the lipid A domain of Acinetobacter baumannii. A. baumannii is a significant, multidrug-resistant, opportunistic pathogen that is particularly difficult to clear from health care settings because of its ability to survive under diverse conditions. LpxS transfers an octanoate (C8:0) fatty acid, the shortest known secondary acyl chain reported to date, replacing a C12:0 fatty acid at the 2' position of lipid A. Expression of LpxS was highly upregulated under cold conditions and likely increases membrane fluidity. Furthermore, incorporation of a C8:0 acyl chain under cold conditions increased the effectiveness of the outer membrane permeability barrier. LpxS orthologs are found in several Acinetobacter species and may represent a common mechanism for adaptation to cold temperatures in these organisms. IMPORTANCE To maintain cellular fitness, the composition of biological membranes must change in response to shifts in temperature or other stresses. This process, known as homeoviscous adaptation, allows for maintenance of optimal fluidity and membrane permeability. Here, we describe an enzyme that alters the fatty acid content of A. baumannii LOS, a major structural feature and key component of the bacterial outer membrane. Although much is known regarding how glycerophospholipids are altered during temperature shifts, our understanding of LOS or LPS alterations under these conditions is lacking. Our work identifies a cold adaptation mechanism in A. baumannii, a highly adaptable and multidrug-resistant pathogen.
Lipopolysaccharide, Lipooligosaccharide, Acinetobacter, Acinetobacter baumannii, lipid A, cell envelope, outer membrane, acylation, acyltransferase, cold shock
NCBI PubMed ID: 34425709Publication DOI: 10.1128/mBio.01295-21Journal NLM ID: 101519231Publisher: Washington, DC: American Society for Microbiology
Correspondence: M. Stephen Trent
Institutions: Department of Infectious Diseases, College of Veterinary Medicine, University of Georgiagrid.213876.9, Athens, Georgia, USA, Department of Microbiology, College of Art and Sciences, University of Georgiagrid.213876.9, Athens, Georgia, USA
Methods: PCR, DNA techniques, TLC, MALDI-TOF MS, radiolabeling, extraction, genome analysis, MIC determination
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12. Compound ID: 15720
|
Lau-(1-3)-R-3HOMyr-(1-2)-+
|
P-4)-+ |
| |
2HOLau-(1-3)-R-3HOMyr-(1-2)-+ | |
| | |
a-Kdop-(2-5)-+ | | |
| | | |
a-Kdop-(2-4)-a-Kdop-(2-6)-b-D-GlcpN-(1-6)-a-D-GlcpN-(1-P
| |
R-3HOLau-(1-3)-+ |
|
R-3HOLau-(1-3)-+ |
Show graphically |
Structure type: oligomer
Compound class: LOS, lipid A
Contained glycoepitopes: IEDB_130650,IEDB_130659,IEDB_135394,IEDB_135515,IEDB_141807,IEDB_150908,IEDB_151531,IEDB_534864
The structure is contained in the following publication(s):
- Article ID: 6068
Herrera CM, Voss BJ, Trent MS "Homeoviscous Adaptation of the Acinetobacter baumannii Outer Membrane: Alteration of Lipooligosaccharide Structure during Cold Stress" -
mBio 12(4) (2021) e0129521
To maintain optimal membrane dynamics, cells from all domains of life must acclimate to various environmental signals in a process referred to as homeoviscous adaptation. Alteration of the lipid composition is critical for maintaining membrane fluidity, permeability of the lipid bilayer, and protein function under diverse conditions. It is well documented, for example, that glycerophospholipid content varies substantially in both Gram-negative and Gram-positive bacteria with changes in growth temperature. However, in the case of Gram-negative bacteria, far less is known concerning structural changes in lipopolysaccharide (LPS) or lipooligosaccharide (LOS) during temperature shifts. LPS/LOS is anchored at the cell surface by the highly conserved lipid A domain and localized in the outer leaflet of the outer membrane. Here, we identified a novel acyltransferase, termed LpxS, involved in the synthesis of the lipid A domain of Acinetobacter baumannii. A. baumannii is a significant, multidrug-resistant, opportunistic pathogen that is particularly difficult to clear from health care settings because of its ability to survive under diverse conditions. LpxS transfers an octanoate (C8:0) fatty acid, the shortest known secondary acyl chain reported to date, replacing a C12:0 fatty acid at the 2' position of lipid A. Expression of LpxS was highly upregulated under cold conditions and likely increases membrane fluidity. Furthermore, incorporation of a C8:0 acyl chain under cold conditions increased the effectiveness of the outer membrane permeability barrier. LpxS orthologs are found in several Acinetobacter species and may represent a common mechanism for adaptation to cold temperatures in these organisms. IMPORTANCE To maintain cellular fitness, the composition of biological membranes must change in response to shifts in temperature or other stresses. This process, known as homeoviscous adaptation, allows for maintenance of optimal fluidity and membrane permeability. Here, we describe an enzyme that alters the fatty acid content of A. baumannii LOS, a major structural feature and key component of the bacterial outer membrane. Although much is known regarding how glycerophospholipids are altered during temperature shifts, our understanding of LOS or LPS alterations under these conditions is lacking. Our work identifies a cold adaptation mechanism in A. baumannii, a highly adaptable and multidrug-resistant pathogen.
Lipopolysaccharide, Lipooligosaccharide, Acinetobacter, Acinetobacter baumannii, lipid A, cell envelope, outer membrane, acylation, acyltransferase, cold shock
NCBI PubMed ID: 34425709Publication DOI: 10.1128/mBio.01295-21Journal NLM ID: 101519231Publisher: Washington, DC: American Society for Microbiology
Correspondence: M. Stephen Trent
Institutions: Department of Infectious Diseases, College of Veterinary Medicine, University of Georgiagrid.213876.9, Athens, Georgia, USA, Department of Microbiology, College of Art and Sciences, University of Georgiagrid.213876.9, Athens, Georgia, USA
Methods: PCR, DNA techniques, TLC, MALDI-TOF MS, radiolabeling, extraction, genome analysis, MIC determination
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13. Compound ID: 15721
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Lau-(1-3)-R-3HOMyr-(1-2)-+
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P-4)-+ |
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2HOLau-(1-3)-R-3HOMyr-(1-2)-+ | |
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a-Kdop-(2-5)-+ | | |
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a-Kdop-(2-4)-a-Kdop-(2-6)-b-D-GlcpN-(1-6)-a-D-GlcpN-(1-P
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Lau-(1-3)-R-3HOLau-(1-3)-+ |
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R-3HOLau-(1-3)-+ |
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Structure type: oligomer
Compound class: LOS, lipid A
Contained glycoepitopes: IEDB_130650,IEDB_130659,IEDB_135394,IEDB_135515,IEDB_141807,IEDB_150908,IEDB_151531,IEDB_534864
The structure is contained in the following publication(s):
- Article ID: 6068
Herrera CM, Voss BJ, Trent MS "Homeoviscous Adaptation of the Acinetobacter baumannii Outer Membrane: Alteration of Lipooligosaccharide Structure during Cold Stress" -
mBio 12(4) (2021) e0129521
To maintain optimal membrane dynamics, cells from all domains of life must acclimate to various environmental signals in a process referred to as homeoviscous adaptation. Alteration of the lipid composition is critical for maintaining membrane fluidity, permeability of the lipid bilayer, and protein function under diverse conditions. It is well documented, for example, that glycerophospholipid content varies substantially in both Gram-negative and Gram-positive bacteria with changes in growth temperature. However, in the case of Gram-negative bacteria, far less is known concerning structural changes in lipopolysaccharide (LPS) or lipooligosaccharide (LOS) during temperature shifts. LPS/LOS is anchored at the cell surface by the highly conserved lipid A domain and localized in the outer leaflet of the outer membrane. Here, we identified a novel acyltransferase, termed LpxS, involved in the synthesis of the lipid A domain of Acinetobacter baumannii. A. baumannii is a significant, multidrug-resistant, opportunistic pathogen that is particularly difficult to clear from health care settings because of its ability to survive under diverse conditions. LpxS transfers an octanoate (C8:0) fatty acid, the shortest known secondary acyl chain reported to date, replacing a C12:0 fatty acid at the 2' position of lipid A. Expression of LpxS was highly upregulated under cold conditions and likely increases membrane fluidity. Furthermore, incorporation of a C8:0 acyl chain under cold conditions increased the effectiveness of the outer membrane permeability barrier. LpxS orthologs are found in several Acinetobacter species and may represent a common mechanism for adaptation to cold temperatures in these organisms. IMPORTANCE To maintain cellular fitness, the composition of biological membranes must change in response to shifts in temperature or other stresses. This process, known as homeoviscous adaptation, allows for maintenance of optimal fluidity and membrane permeability. Here, we describe an enzyme that alters the fatty acid content of A. baumannii LOS, a major structural feature and key component of the bacterial outer membrane. Although much is known regarding how glycerophospholipids are altered during temperature shifts, our understanding of LOS or LPS alterations under these conditions is lacking. Our work identifies a cold adaptation mechanism in A. baumannii, a highly adaptable and multidrug-resistant pathogen.
Lipopolysaccharide, Lipooligosaccharide, Acinetobacter, Acinetobacter baumannii, lipid A, cell envelope, outer membrane, acylation, acyltransferase, cold shock
NCBI PubMed ID: 34425709Publication DOI: 10.1128/mBio.01295-21Journal NLM ID: 101519231Publisher: Washington, DC: American Society for Microbiology
Correspondence: M. Stephen Trent
Institutions: Department of Infectious Diseases, College of Veterinary Medicine, University of Georgiagrid.213876.9, Athens, Georgia, USA, Department of Microbiology, College of Art and Sciences, University of Georgiagrid.213876.9, Athens, Georgia, USA
Methods: PCR, DNA techniques, TLC, MALDI-TOF MS, radiolabeling, extraction, genome analysis, MIC determination
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14. Compound ID: 15886
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Lau-(1-3)-3HOLau-(1-3)-+ 3HOMyr-(1-2)-+
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3HOMyr-(1-3)-3HOLau-(1-2)-b-D-GlcpN-(1-6)-a-D-GlcpN-(1-P
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P-4)-+ 3HOLau-(1-3)-+ |
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Structure type: oligomer
Compound class: lipid A
Contained glycoepitopes: IEDB_135394,IEDB_135515,IEDB_141807,IEDB_151531,IEDB_534864
The structure is contained in the following publication(s):
- Article ID: 6152
Troudi A, Pagès JM, Brunel JM "Chemical Highlights Supporting the Role of Lipid A in Efficient Biological Adaptation of Gram-Negative Bacteria to External Stresses" -
Journal of Medicinal Chemistry 64(4) (2021) 1816-1834
The outer membrane (OM) of Gram-negative bacteria provides an efficient barrier against external noxious compounds such as antimicrobial agents. Associated with drug target modification, it contributes to the overall failure of chemotherapy. In the complex OM architecture, Lipid A plays an essential role by anchoring the lipopolysaccharide in the membrane and ensuring the spatial organization between lipids, proteins, and sugars. Currently, the targets of almost all antibiotics are intracellularly located and require translocation across membranes. We report herein an integrated view of Lipid A synthesis, membrane assembly, a structure comparison at the molecular structure level of numerous Gram-negative bacterial species, as well as its recent use as a target for original antibacterial molecules. This review paves the way for a new vision of a key membrane component that acts during bacterial adaptation to environmental stresses and for the development of new weapons against microbial resistance to usual antibiotics.
Lipopolysaccharide, lipid A, Gram-negative bacteria, outer membrane, stress, adaptation
NCBI PubMed ID: 33538159Publication DOI: 10.1021/acs.jmedchem.0c02185Journal NLM ID: 9716531Publisher: Washington, DC: American Chemical Society
Correspondence: bruneljm@yahoo.fr
Institutions: UMR-MD1, U1261, Aix Marseille Université, INSERM, SSA, MCT, 13385 Marseille, France, Laboratory of Microorganisms and Active Biomolecules, Department of Biology, Faculty of Sciences of Tunis, University of Tunis El Manar, Tunis 1008, Tunisia
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15. Compound ID: 16423
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Lau-(1-3)-3HOMyr-(1-2)-+
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Lau-(1-3)-R-3HOLau-(1-3)-+ |
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R-3HOMyr-(1-3)-R-3HOLau-(1-2)-b-D-GlcpN-(1-6)-a-D-GlcpN-(1-P
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P-4)-+ |
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R-3HOLau-(1-3)-+ |
Show graphically |
Structure type: oligomer
Compound class: lipid A
Contained glycoepitopes: IEDB_135394,IEDB_135515,IEDB_141807,IEDB_151531,IEDB_534864
The structure is contained in the following publication(s):
- Article ID: 6385
Fux AC, Casonato Melo C, Michelini S, Swartzwelter BJ, Italiani P, Himly M "Heterogeneity of Lipopolysaccharide as Source of Variability in Bioassays and LPS-Binding Proteins as Remedy" -
International Journal of Molecular Sciences 24(9) (2023) 8395
Lipopolysaccharide (LPS), also referred to as endotoxin, is the major component of Gram-negative bacteria's outer cell wall. It is one of the main types of pathogen-associated molecular patterns (PAMPs) that are known to elicit severe immune reactions in the event of a pathogen trespassing the epithelial barrier and reaching the bloodstream. Associated symptoms include fever and septic shock, which in severe cases, might even lead to death. Thus, the detection of LPS in medical devices and injectable pharmaceuticals is of utmost importance. However, the term LPS does not describe one single molecule but a diverse class of molecules sharing one common feature: their characteristic chemical structure. Each bacterial species has its own pool of LPS molecules varying in their chemical composition and enabling the aggregation into different supramolecular structures upon release from the bacterial cell wall. As this heterogeneity has consequences for bioassays, we aim to examine the great variability of LPS molecules and their potential to form various supramolecular structures. Furthermore, we describe current LPS quantification methods and the LPS-dependent inflammatory pathway and show how LPS heterogeneity can affect them. With the intent of overcoming these challenges and moving towards a universal approach for targeting LPS, we review current studies concerning LPS-specific binders. Finally, we give perspectives for LPS research and the use of LPS-binding molecules.
Lipopolysaccharide, lipid A, immunology, endotoxin, detection, low endotoxin recovery, LPS-binding molecules
NCBI PubMed ID: 37176105Publication DOI: 10.3390/ijms24098395Journal NLM ID: 101092791Publisher: Basel, Switzerland: MDPI
Correspondence: M. Himly
Institutions: Division of Allergy & Immunology, Department of Biosciences & Medical Biology, Paris Lodron University of Salzburg (PLUS), Hellbrunnerstra?e 34, 5020 Salzburg, Austria, Chemical Biology Department, R&D Reagents, Miltenyi Biotec B.V. & Co. KG, Friedrich-Ebert-Straße 68, 51429 Bergisch Gladbach, Germany, Biotechnical Faculty, Department of Biology, University of Ljubljana, Večna pot 111, 1000 Ljubljana, Slovenia, Department of Microbiology, Immunology, and Pathology, 1601 Campus Delivery, Colorado State University, Fort Collins, CO 80523, USA, Experimental Medical Physics, Heinrich-Heine University Düsseldorf, Universitätsstraße 1, 40225 Düsseldorf, Germany, Institute of Biochemistry and Cell Biology, Consiglio Nazionale delle Ricerche (CNR), Via P. Castellino 111, 80131 Naples, Italy, Stazione Zoologica Anton Dohrn (SZN), Villa Comunale, 80121 Naples, Italy
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Total list of corresponding CSDB IDs (permanent record IDs):
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