| 1. |
- Barone, Angela, et al.
(författare)
-
Evaluation of Sialyl-Lactotetra as a Marker for Epithelial Ovarian Tumors
- 2020
-
Ingår i: Frontiers in Oncology. - : Frontiers Media SA. - 2234-943X. ; 10
-
Tidskriftsartikel (refereegranskat)abstract
- Ovarian carcinoma is a heterogeneous disease with distinct molecular and histological profiles, ranging from low grade atypia to highly aggressive tumors associated with a poor prognosis. In the present study, glycosphingolipids were isolated from human high-grade serous ovarian carcinoma, whereby the novel stem cell marker Sialyl-lactotetra (S-Lc(4)) was characterized in two out of three cases. The presence and level of S-Lc(4)was further evaluated immunohistochemically in a cohort of patients with ovarian tumors ranging from benign lesions to high grade serous carcinoma (n= 478). Its expression was assessed in association with tumor grade, stage, histology, and survival. The data showed that S-Lc(4)is most common and highly expressed in borderline type tumors and carcinomas with low levels of aggressiveness, such as mucinous, endometrioid, and low grade serous. Accordingly, S-Lc(4)-positivity was associated with better disease-free survival. The expression of S-Lc(4)was seemingly associated with lineage continuity and could be traced from premalignant lesions to carcinoma, suggesting inheritance by a stem cell lineage that gives rise to generally indolent tumors.
|
|
| 2. |
- Benktander, John, et al.
(författare)
-
Aeromonas salmonicida binds α2-6 linked sialic acid, which is absent among the glycosphingolipid repertoires from skin, gill, stomach, pyloric caecum, and intestine
- 2022
-
Ingår i: Virulence. - : Informa UK Limited. - 2150-5594 .- 2150-5608. ; 13:1, s. 1741-1751
-
Tidskriftsartikel (refereegranskat)abstract
- Carbohydrates can both protect against infection and act as targets promoting infection. Mucins are major components of the slimy mucus layer covering the fish epithelia. Mucins can act as decoys for intimate pathogen interaction with the host afforded by binding to glycosphingolipids in the host cell membrane. We isolated and characterized glycosphingolipids from Atlantic salmon skin, gill, stomach, pyloric caeca, and intestine. We characterized the glycosphingolipids using liquid chromatography–mass spectrometry and tandem mass spectrometry and the glycan repertoire was compared with the glycan repertoire of mucins from the same epithelia. We also investigated Aeromonas salmonicida binding using chromatogram and microtiter well based binding assays. We identified 29 glycosphingolipids. All detected acid glycans were of the ganglio-series (unless shorter) and showed a high degree of polysialylation. The non-acid glycans were mostly composed of the neolacto, globo, and ganglio core structures. The glycosphingolipid repertoire differed between epithelia and the proportion of the terminal moieties of the glycosphingolipids did not reflect the terminal moieties on the mucins from the same epithelia. A. salmonicida did not bind the Atlantic salmon glycosphingolipids. Instead, we identified that A. salmonicida binding to sialic acid occurred to α2–6 Neu5Ac but not to α2–3 Neu5Ac. α2–6 Neu5Ac was present on mucins whereas mainly α2–3 Neu5Ac was found on the glycosphingolipids, explaining the difference in A. salmonicida binding ability between these host glycoconjugates. A. salmonicida´s ability to bind to Atlantic salmon mucins, but not the glycosphingolipids, is likely part of the host defence against this pathogen.
|
|
| 3. |
- Esberg, Anders, et al.
(författare)
-
Corynebacterium matruchotii Demography and Adhesion Determinants in the Oral Cavity of Healthy Individuals
- 2020
-
Ingår i: Microorganisms. - : MDPI. - 2076-2607. ; 8:11
-
Tidskriftsartikel (refereegranskat)abstract
- Corynebacterium matruchotii may be key in tooth biofilm formation, but information about demographics, bacterial partners, and binding ligands is limited. The aims of this study were to explore C. matruchotii's demography by age and colonization site (plaque and saliva), in vitro bacterial-bacterial interactions in coaggregation and coadhesion assays, and glycolipids as potential binding ligands in thin-layer chromatogram binding assays. C. matruchotii prevalence increased from 3 months to 18 years old, with 90% and 100% prevalence in saliva and tooth biofilm, respectively. C. matruchotii aggregated in saliva in a dose-dependent manner but lacked the ability to bind to saliva-coated hydroxyapatite. In vivo, C. matruchotii abundance paralleled that of Actinomyces naeslundii, Capnocytophaga sp. HMT 326, Fusobacterium nucleatum subsp. polymorphum, and Tannerella sp. HMT 286. In vitro, C. matruchotii bound both planktonic and surface-bound A. naeslundii, Actinomyces odontolyticus, and F. nucleatum. In addition, C. matruchotii exhibited the ability to bind glycolipids isolated from human erythrocytes (blood group O), human granulocytes, rabbit intestine, human meconium, and rat intestine. Binding assays identified candidate carbohydrate ligands as isoglobotriaosylceramide, Gal alpha 3-isoglobotriaosylceramide, lactotriaosylceramide, lactotetraosylceramide, neolactotetraosylceramide, and neolactohexaosylceramide. Thus, C. matruchotii likely uses specific plaque bacteria to adhere to the biofilm and may interact with human tissues through carbohydrate interactions.
|
|
| 4. |
- Horejsi, K., et al.
(författare)
-
Comprehensive characterization of complex glycosphingolipids in human pancreatic cancer tissues
- 2023
-
Ingår i: Journal of Biological Chemistry. - : Elsevier BV. - 0021-9258. ; 299:3
-
Tidskriftsartikel (refereegranskat)abstract
- Pancreatic ductal adenocarcinoma (PDAC) is one of the most common causes of cancer-related deaths worldwide, accounting for 90% of primary pancreatic tumors with an average 5-year survival rate of less than 10%. PDAC exhibits aggressive biology, which, together with late detection, results in most PDAC patients presenting with unresectable, locally advanced, or metastatic disease. In-depth lipid profiling and screening of potential biomarkers currently appear to be a promising approach for early detection of PDAC or other cancers. Here, we isolated and characterized complex glycosphingolipids (GSL) from normal and tumor pancreatic tissues of patients with PDAC using a combination of TLC, chemical staining, carbohydrate-recognized ligand-binding assay, and LC/ESIMS2. The major neutral GSL identified were GSL with the terminal blood groups A, B, H, Lea, Leb, Lex, Ley, P1, and PX2 determinants together with globo- (Gb3 and Gb4) and neolactoseries GSL (nLc4 and nLc6). We also revealed that the neutral GSL profiles and their relative amounts differ between normal and tumor tissues. Additionally, the normal and tumor pancreatic tissues differ in type 1/2 core chains. Sulfatides and GM3 gangliosides were the predominant acidic GSL along with the minor sialyl-nLc4/nLc6 and sialyl-Lea/Lex. The comprehensive analysis of GSL in human PDAC tissues extends the GSL coverage and provides an important platform for further studies of GSL alterations; therefore, it could contribute to the development of new biomarkers and therapeutic approaches.
|
|
| 5. |
- Jin, Chunsheng, et al.
(författare)
-
Characterization of novel nonacid glycosphingolipids as biomarkers of human gastric adenocarcinoma
- 2022
-
Ingår i: Journal of Biological Chemistry. - : Elsevier BV. - 0021-9258 .- 1083-351X. ; 298:4
-
Tidskriftsartikel (refereegranskat)abstract
- degenerative changes appear leading to premalignant conditions as atrofic gastritis, metaplasia, and dysplasia. binding of bacterial adhesins to carbohydrate receptors on the gastric epithelium. A number of different carbohydrate receptor been reported (reviewed in Ref. (2)). Despite the multitude of candidate H. pylori glycan receptors, only three carbohydratebinding adhesins have been characterized to date; the blood group antigen-binding BabA adhesin, the sialic acid-binding SabA adhesin, and the LabA adhesin (reviewed in Ref. (3)). adhesin BabA (4). H. pylori strains expressing BabA together with VacA and CagA (triple-positive strains) are highly associated with severe gastric diseases, as peptic ulcer or gastric adenocarcinoma. BabA mediates the initial attachment of H. pylori to the human gastric mucosa. The first observation recognized by H. pylori BabA was followed by a division of BabA-producing H. pylori strains into specialist and generalist strains, depending on their mode of binding to Leb and related carbohydrate sequences (5). BabA of specialist strains binds
|
|
| 6. |
- Madar Johansson, Miralda, et al.
(författare)
-
Glycosphingolipids Recognized by Acinetobacter baumannii
- 2020
-
Ingår i: Microorganisms. - : MDPI AG. - 2076-2607. ; 8:4
-
Tidskriftsartikel (refereegranskat)abstract
- Acinetobacter baumannii is an opportunistic bacterial pathogen associated with hospital-acquired infections, including pneumonia, meningitis, bacteremia, urinary tract infection, and wound infections. Recognition of host cell surface carbohydrates plays a crucial role in adhesion and enables microbes to colonize different host niches. Here the potential glycosphingolipid receptors of A. baumannii were examined by binding of S-35-labeled bacteria to glycosphingolipids on thin-layer chromatograms. Thereby a selective interaction with two non-acid glycosphingolipids of human and rabbit small intestine was found. The binding-active glycosphingolipids were isolated and, on the basis of mass spectrometry, identified as neolactotetraosylceramide (Gal beta 4GlcNAc beta 3Gal beta 4Glc beta 1Cer) and lactotetraosylceramide (Gal beta 3GlcNAc beta 3Gal beta 4Glc beta 1Cer). Further binding assays using reference glycosphingolipids showed that A. baumannii also bound to lactotriaosylceramide (GlcNAc beta 3Gal beta 4Glc beta 1Cer) demonstrating that GlcNAc was the basic element recognized. In addition, the bacteria occasionally bound to galactosylceramide, lactosylceramide with phytosphingosine and/or hydroxy fatty acids, isoglobotriaosylceramide, gangliotriaosylceramide, and gangliotetraosylceramide, in analogy with binding patterns that previously have been described for other bacteria classified as "lactosylceramide-binding". Finally, by isolation and characterization of glycosphingolipids from human skin, the presence of neolactotetraosylceramide was demonstrated in this A. baumannii target tissue.
|
|
| 7. |
- Madar Johansson, Miralda, et al.
(författare)
-
The binding mechanism of the virulence factor Streptococcus suis adhesin P subtype to globotetraosylceramide is associated with systemic disease
- 2020
-
Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 295:42, s. 14305-14324
-
Tidskriftsartikel (refereegranskat)abstract
- Streptococcus suis is part of the pig commensal microbiome but strains can also be pathogenic, causing pneumonia and meningitis in pigs as well as zoonotic meningitis. According to genomic analysis, S. suis is divided into asymptomatic carriage, respiratory and systemic strains with distinct genomic signatures. Because the strategies to target pathogenic S. suis are limited, new therapeutic approaches are needed. The virulence factor S. suis adhesin P (SadP) recognizes the galabiose Gal alpha 1-4Gal-oligosaccharide. Based on its oligosaccharide fine specificity, SadP can be divided into subtypes P-N and P-O. We show here that subtype P-N is distributed in the systemic strains causing meningitis, whereas type P-O is found in asymptomatic carriage and respiratory strains. Both types of SadP are shown to predominantly bind to pig lung globotriaosylceramide (Gb3). However, SadP adhesin from systemic subtype P-N strains also binds to globotetraosylceramide (Gb4). Mutagenesis studies of the galabiose-binding domain of type P-N SadP adhesin showed that the amino acid asparagine 285, which is replaced by an aspartate residue in type P-O SadP, was required for binding to Gb4 and, strikingly, was also required for interaction with the glycomimetic inhibitor phenylurea-galabiose. Molecular dynamics simulations provided insight into the role of Asn-285 for Gb4 and phenylurea-galabiose binding, suggesting additional hydrogen bonding to terminal GalNAc of Gb4 and the urea group. Thus, the Asn-285-mediated molecular mechanism of type P-N SadP binding to Gb4 could be used to selectively target S. suis in systemic disease without interfering with commensal strains, opening up new avenues for interventional strategies against this pathogen.
|
|
| 8. |
- Quintana-Hayashi, Macarena P, et al.
(författare)
-
Porcine intestinal glycosphingolipids recognized by Brachyspira hyodysenteriae
- 2023
-
Ingår i: Microbial Pathogenesis. - : Elsevier BV. - 0882-4010. ; 175
-
Tidskriftsartikel (refereegranskat)abstract
- Swine dysentery caused by Brachyspira hyodysenteriae is a disease present worldwide with an important economic impact on the farming business, resulting in an increased use of antibiotics. In the present study, we investigated the binding of B. hyodysenteriae to glycosphingolipids from porcine small intestinal epithelium in order to determine the glycosphingolipids involved in B. hyodysenteriae adhesion. Specific interactions between B. hyodysenteriae and two non-acid glycosphingolipids were obtained. These binding-active glycosphingolipids, were characterized by mass spectrometry as lactotetraosylceramide (Galβ3GlcNAcβ3Galβ4Glcβ1Cer) and the B5 glycosphingolipid (Galα3Galβ4GlcNAcβ3Galβ4Glcβ1Cer). Comparative binding studies using structurally related reference glycosphingolipids showed that B. hyodysenteriae binding to lactotetraosylceramide required an unsubstituted terminal Galβ3GlcNAc sequence, while for binding to the B5 pentaosylceramide the terminal Galα3Galβ4GlcNAc sequence is the minimum element recognized by the bacteria. Binding of Griffonia simplicifolia IB4 lectin to pig colon tissue sections from healthy control pig and B. hyodysenteriae infected pigs showed that in the healthy pigs the Galα3Gal epitope was mainly present in the lamina propria. In contrast, in four out of five pigs with swine dysentery there was an increased expression of Galα3Gal in the goblet cells and in the colonic crypts, where B. hyodysenteriae also was present. The one pig that had recovered by the time of necropsy had the Galα3Gal epitope only in the lamina propria. These data are consistent with a model where a transient increase in the carbohydrate sequence recognized by the bacteria occur in colonic mucins during B. hyodysenteriae infection, suggesting that the mucins may act as decoys contributing to clearance of the infection. These findings may lead to novel strategies for treatment of B. hyodysenteriae induced swine dysentery.
|
|
| 9. |
- Santos, Licínia, et al.
(författare)
-
Characterization of glycosphingolipids from gastrointestinal stromal tumours.
- 2020
-
Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
-
Tidskriftsartikel (refereegranskat)abstract
- Gastrointestinal stromal tumours (GISTs) are the major nonepithelial neoplasms of the human gastrointestinal tract with a worldwide incidence between 11 and 15 per million cases annually. In this study the acid and non-acid glycosphingolipids of three GISTs were characterized using a combination of thin-layer chromatography, chemical staining, binding of carbohydrate recognizing ligands, and mass spectrometry. In the non-acid glycosphingolipid fractions of the tumors globotetraosylceramide, neolactotetraosylceramide, and glycosphingolipids with terminal blood group A, B, H, Lex, Lea, Ley and Leb determinants were found. The relative amounts of these non-acid compounds were different in the three tumour samples. The acid glycosphingolipid fractions had sulfatide, and the gangliosides GM3, GD3, GM1, Neu5Acα3neolactotetraosylceramide, GD1a, GT1b and GQ1b. In summary, we have characterized the glycosphingolipids of GISTs and found that the pattern differs in tumours from different individuals. This detailed characterization of glycosphingolipid composition of GISTs could contribute to recognition of new molecular targets for GIST treatment and sub-classification.
|
|
| 10. |
- Santos, Licínia, et al.
(författare)
-
Characterization of sheep erythrocyte glycosphingolipids recognized by human anti-Forssman antibodies.
- 2020
-
Ingår i: Glycobiology. - : Oxford University Press (OUP). - 1460-2423. ; 30:11, s. 881-894
-
Tidskriftsartikel (refereegranskat)abstract
- The FORS histo-blood group system is the most recently discovered carbohydrate-based human blood group system. FORS is a rare blood group system, and most individuals have naturally occurring anti-FORS1 antibodies in plasma. Screening for anti-FORS1 antibodies is often done by hemagglutination assays using FORS1-expressing sheep erythrocytes, since FORS1-positive human erythrocytes are most often not available. Here, we have characterized the non-acid glycosphingolipids from sheep erythrocytes and isolated subfractions, with mass spectrometry, binding of antibodies and lectins, and by enzymatic hydrolysis. This demonstrated the presence of Forssman and Galili pentaosylceramides, and a Galili heptaosylceramide. Two complex glycosphingolipids recognized by human anti-FORS1 antibodies were characterized as a Forssman neolacto hybrid hexaosylceramide (GalNAcα3GalNAcβ3Galβ4GlcNAcβ3Galβ4Glcβ1Cer) and a Forssman Galili hybrid heptaosylceramide (GalNAcα3GalNAcβ3Galα3Galβ4GlcNAcβ3Galβ4Glcβ1Cer). These are novel glycosphingolipid structures, and to our knowledge, the first case of an elongated Galili antigen. Thus, the anti-Forssman antibodies in human serum bind not only to the classical Forssman pentaosylceramide (GalNAcα3GalNAcβ3Galα4Galβ4Glcβ1Cer), but also when the GalNAcα3GalNAcβ3 sequence is presented on a neolacto core chain and even on a Galili carbohydrate sequence.
|
|
