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- Chahal, Gurdeep, et al.
(författare)
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A Complex Connection Between the Diversity of Human Gastric Mucin O-Glycans, Helicobacter pylori Binding, Helicobacter Infection and Fucosylation
- 2022
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Ingår i: Molecular & Cellular Proteomics. - : Elsevier BV. - 1535-9476 .- 1535-9484. ; 21:11
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Tidskriftsartikel (refereegranskat)abstract
- Helicobacter pylori colonizes the stomach of half of the human population. Most H. pylori are located in the mucus layer, which is mainly comprised by glycosylated mucins. Using mass spectrometry, we identified 631 glycans (whereof 145 were fully characterized and the remainder assigned as compositions) on mucins isolated from 14 Helicobacter spp.-infected and 14 Helicobacter spp.-noninfected stomachs. Only six identified glycans were common to all individuals, from a total of 60 to 189 glycans in each individual. An increased number of unique glycan structures together with an increased intra-individual diversity and larger interindividual variation were identified among O-glycans from Helicobacter spp.-infected stomachs compared with noninfected stom-achs. H. pylori strain J99, which carries the blood group antigen-binding adhesin (BabA), the sialic acid-binding adhesin (SabA), and the LacdiNAc-binding adhesin, bound both to Lewis b (Leb)-positive and Leb-negative mucins. Among Leb-positive mucins, H. pylori J99 bind-ing was higher to mucins from Helicobacter spp.-infected individuals than noninfected individuals. Statistical corre-lation analysis, binding experiments with J99 wt, and J99 Delta babA Delta sabA and inhibition experiments using syn-thetic glycoconjugates demonstrated that the differences in H. pylori-binding ability among these four groups were governed by BabA-dependent binding to fucosylated structures. LacdiNAc levels were lower in mucins that bound to J99 lacking BabA and SabA than in mucins that did not, suggesting that LacdiNAc did not significantly contribute to the binding. We identified 24 O-glycans from Leb-negative mucins that correlated well with H. pylori binding whereof 23 contained alpha 1,2-linked fucosylation. The large and diverse gastric glycan library identified, including structures that correlated with H. pylori binding, could be used to select glycodeterminants to experimen-tally investigate further for their importance in host- pathogen interactions and as candidates to develop glycan-based therapies.
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| 3. |
- Chahal, Gurdeep, et al.
(författare)
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Streptococcus oralis Employs Multiple Mechanisms of Salivary Mucin Binding That Differ Between Strains
- 2022
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Ingår i: Frontiers in Cellular and Infection Microbiology. - : Frontiers Media SA. - 2235-2988. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Streptococcus oralis is an oral commensal and opportunistic pathogen that can enter the bloodstream and cause bacteremia and infective endocarditis. Here, we investigated the mechanisms of S. oralis binding to oral mucins using clinical isolates, isogenic mutants and glycoconjugates. S. oralis bound to both MUC5B and MUC7, with a higher level of binding to MUC7. Mass spectrometry identified 128 glycans on MUC5B, MUC7 and the salivary agglutinin (SAG). MUC7/SAG contained a higher relative abundance of Lewis type structures, including Lewis b/y, sialyl-Lewis a/x and alpha 2,3-linked sialic acid, compared to MUC5B. S. oralis subsp. oralis binding to MUC5B and MUC7/SAG was inhibited by Lewis b and Lacto-N-tetraose glycoconjugates. In addition, S. oralis binding to MUC7/SAG was inhibited by sialyl Lewis x. Binding was not inhibited by Lacto-N-fucopentaose, H type 2 and Lewis x conjugates. These data suggest that three distinct carbohydrate binding specificities are involved in S. oralis subsp. oralis binding to oral mucins and that the mechanisms of binding MUC5B and MUC7 differ. Efficient binding of S. oralis subsp. oralis to MUC5B and MUC7 required the gene encoding sortase A, suggesting that the adhesin(s) are LPXTG-containing surface protein(s). Further investigation demonstrated that one of these adhesins is the sialic acid binding protein AsaA.
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- Patel, Kush P., et al.
(författare)
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Health Care Resource, Economic, and Readmission Implications After Acute Decompensated Aortic Stenosis–A Nationwide Study
- 2023
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Ingår i: American Journal of Cardiology. - 0002-9149. ; 204, s. 200-206
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Tidskriftsartikel (refereegranskat)abstract
- Acute decompensated aortic stenosis (ADAS) is common. The cumulative burden of ADAS from a clinical, health care resource, and financial perspective is unknown. This study sought to assess the national impact of ADAS compared with electively treated, stable patients with aortic stenosis (non-ADAS). Using the National Readmissions Database between 2016 and 2019, patients with ADAS and non-ADAS were identified using International Classification of Diseases, Tenth Revision codes. Patients with ADAS were propensity-matched to non-ADAS patients (1:2) using age, gender, and Charlson co-morbidity index. We compared in-hospital mortality, length of stay (LOS), health care–associated costs, and 90-day readmission data between the 2 cohorts. A total of 51,498 propensity-matched patients were included in this study: median age 75 years, 64% men. The in-hospital mortality for ADAS was higher than non-ADAS (2.8% vs 1.5%, p <0.0001). The LOS during the index admission was longer for ADAS (9 [5 to 13] vs 4 [2 to 6] days, p <0.0001). The health care–associated costs per patient was greater for ADAS ($55,450.0 [41,860.4 to 74,500.7] vs $43,405.7 [34,218.5 to 56,034.8], p <0.0001). Readmission to hospital within 90 days was more frequent in ADAS (21.1 vs 16.8%, p <0.001). The in-hospital mortality during readmission was higher with ADAS (3.9% vs 2.8%, p = 0.004). The readmission LOS was longer with ADAS (4 [2 to 7] vs 3 [2 to 6] days, p <0.0001). In conclusion, ADAS imposes a significant burden clinically and financially and on health care resources compared with non-ADAS during the index admission and 90-day follow-up. There is an urgent need to predict ADAS and optimize the timing of aortic valve replacement to reduce the incidence and the burden associated with ADAS.
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