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- Madar Johansson, Miralda, et al.
(author)
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The binding mechanism of the virulence factor Streptococcus suis adhesin P subtype to globotetraosylceramide is associated with systemic disease
- 2020
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In: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 295:42, s. 14305-14324
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Journal article (peer-reviewed)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.
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| 3. |
- Sever, Mehmet Sukru, et al.
(author)
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A roadmap for optimizing chronic kidney disease patient care and patient-oriented research in the Eastern European nephrology community
- 2021
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In: Clinical Kidney Journal. - : Oxford University Press. - 2048-8505 .- 2048-8513. ; 14:1, s. 23-35
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Research review (peer-reviewed)abstract
- Chronic kidney disease (CKD) is a major health problem because of its high prevalence, associated complications and high treatment costs. Several aspects of CKD differ significantly in the Eastern European nephrology community compared with Western Europe because of different geographic, socio-economic, infrastructure, cultural and educational features. The two most frequent aetiologies of CKD, DM and hypertension, and many other predisposing factors, are more frequent in the Eastern region, resulting in more prevalent CKD Stages 3-5. Interventions may minimize the potential drawbacks of the high prevalence of CKD in Eastern Europe, which include several options at various stages of the disease, such as raising public, medical personnel and healthcare authorities awareness; early detection by screening high-risk populations; preventing progression and CKD-related complications by training health professionals and patients; promoting transplantation or home dialysis as the preferred modality; disseminating and implementing guidelines and guided therapy and encouraging/supporting country-specific observational research as well as international collaborative projects. Specific ways to significantly impact CKD-related problems in every region of Europe through education, science and networking are collaboration with non-nephrology European societies who have a common interest in CKD and its associated complications, representation through an advisory role within nephrology via national nephrology societies, contributing to the training of local nephrologists and stimulating patient-oriented research. The latter is mandatory to identify country-specific kidney disease-related priorities. Active involvement of patients in this research via collaboration with the European Kidney Patient Federation or national patient federations is imperative to ensure that projects reflect specific patient needs.
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| 4. |
- Derner, Ondrej, et al.
(author)
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Incidence of Kidney Replacement Therapy and Subsequent Outcomes Among Patients With Systemic Lupus Erythematosus : Findings From the ERA Registry
- 2022
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In: American Journal of Kidney Diseases. - : Elsevier BV. - 0272-6386. ; 79:5, s. 635-645
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Journal article (peer-reviewed)abstract
- Rationale & Objective: There is a dearth of data characterizing patients receiving kidney replacement therapy (KRT) for kidney failure due to systemic lupus erythematosus (SLE) and their clinical outcomes. The aim of this study was to describe trends in incidence and prevalence of KRT among these patients as well as to compare their outcomes versus those of patients treated with KRT for diseases other than SLE. Study Design: Retrospective cohort study based on kidney registry data. Setting & Participants: Patients recorded in 14 registries of patients receiving KRT that provided data to the European Renal Association Registry between 1992 and 2016. Predictor: SLE as cause of kidney failure. Outcomes: Incidence and prevalence of KRT, patient survival while receiving KRT, patient and graft survival after kidney transplant, and specific causes of death. Analytical Approach: Kaplan-Meier methods and Cox regression models were fit to compare patient survival between the SLE and non-SLE groups, overall KRT, dialysis, and patient and graft survival after kidney transplant. Results: In total, 1,826 patients commenced KRT for kidney failure due to SLE, representing an incidence of 0.80 per million population (pmp) per year. The incidence remained stable during the study period (annual percent change, 0.1% [95% CI, −0.6% to 0.8%]). Patient survival among patients with SLE receiving KRT was similar to survival in the comparator group (hazard ratio [HR], 1.11 [95% CI, 0.99-1.23]). After kidney transplant, the risk of death was greater among patients with SLE than among patients in the comparator group (HR, 1.25 [95% CI, 1.02-1.53]), whereas the risk of all-cause graft failure was similar (HR, 1.09 [95% CI, 0.95-1.27]). Ten-year patient overall survival during KRT and patient and graft survival after kidney transplant improved over the study period (HRs of 0.71 [95% CI, 0.56-0.91], 0.43 [95% CI, 0.27-0.69], and 0.60 [95% CI, 0.43-0.84], respectively). Patients with SLE receiving KRT were significantly more likely to die of infections (24.8%) than patients in the comparator group (16.9%; P < 0.001). Limitations: No data were available on extrarenal manifestations of SLE, drug treatments, comorbidities, kidney transplant characteristics, or relapses of SLE. Conclusions: The prognosis of patients with SLE receiving KRT has improved over time. Survival of patients with SLE who required KRT was similar compared with patients who required KRT for other causes of kidney failure. Survival following kidney transplants was worse among patients with SLE.
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