bims-supasi 2026-03-22 papers

bims-supasi

Biomed News

on Sulfation pathways and signalling

Issue of 2026–03–22
eleven papers selected by
Jonathan Wolf Mueller, University of Birmingham

Chondroitin sulfate degradation bolsters Proteus mirabilis growth and colonization of the catheterized urinary tract.
Degradation and utilization of chondroitin sulfate with different molecular weights by the gut microbiota from four midlife women: Role of Bacteroides ovatus AP1.
Glycoinformatic profiling of label-free intact heparan sulfate oligosaccharides.
Controllable peroxidase-like catalysis of chondroitin sulfate-hemin conjugates for in situ hydrogel formation in biomedical applications.
Inhibition of Dermatan Sulfate Epimerase 1 by Substituted Glucuronic Acids.
Effect of Normothermic Machine Perfusion on Glycocalyx Shedding During Liver Transplantation - A Prospective Pilot Study.
Host-derived nitrate fuels indole production by Escherichia coli to drive chronic kidney disease progression.
Sulfated Exopolysaccharides from Porphyridium purpureum: A Review of Extraction, Structural Characterization, and Chemical Properties for Advanced Applications.
Advances in fucoidan extraction and structure-bioactivity relationships.
Neuroprotective response against the onset of ischemic stroke by upregulation of histone H3Y99 sulfation.
Integrative analysis of sulfate transporters in Citrus sinensis reveals CsSULTR3;5 involved in pathogen stress response.

bioRxiv. 2026 Mar 02. pii: 2026.03.02.708568. [Epub ahead of print]

Chondroitin sulfate degradation bolsters Proteus mirabilis growth and colonization of the catheterized urinary tract.

Benjamin C Hunt, Vitus Brix, Namrata Deka, Brian S Learman, Aimee L Brauer, Brianna M Shipman, Nicole De Nisco, Chelsie E Armbruster.

Glycosaminoglycans (GAGs) are negatively charged polysaccharides composed of repeating disaccharide units and are essential components of the extracellular matrix throughout numerous tissues. The bladder urothelium has a thick protective GAG layer that primarily consists of chondroitin sulfate (CS), heparan sulfate (HS), and hyaluronic acid (HA), and urinary tract pathogens must either degrade or otherwise circumvent this layer to infect the urothelium. In this study, we investigated GAG degradation by Proteus mirabilis, a common and persistent colonizer of the catheterized urinary tract. Almost all P. mirabilis urinary tract isolates harbor a putative chondroitin endolyase (PMI2127), exolyase (PMI2128), and sulfatase (PMI2124). By generating mutant and complemented strains of these genes, we determined that P. mirabilis strain HI4320 degrades multiple forms of CS under numerous culture conditions, including during growth in human urine, and can use CS degradation products as a carbon source. Sulfatase and endolyase activity were required for efficient degradation of all CS types, while the exolyase only contributed to using CS-B or CS-C as carbon source. Interestingly, only endolyase activity contributed to colonization in a murine model of CAUTI, although the colonization defect was even more pronounced when the endolyase and exolyase were both disrupted. The colonization defect was specific to the CAUTI model, likely due to the impact of catheterization on the GAG landscape of the bladder. Limiting CS degradation by P. mirabilis may therefore represent a strategy for reducing risk of ascending infection in catheterized patients.
Importance: Glycosaminoglycans (GAGs) are a family of negatively charged heteropolysaccharides that are ubiquitously expressed throughout the body, forming a significant component of the extracellular matrix and a luminal GAG layer in the bladder. This GAG layer functions as a physical barrier for the bladder surface, protecting it from bacterial infection. Disruption of this barrier through physical forces, such as catheter insertion, or enzymatic degradation by bacteria may contribute to infection outcomes. In this study, we defined the contribution of three putative chondroitin sulfate degrading enzymes (PMI2124, PMI2127, PMI2128) to the pathogenesis of a common pathogen in the catharized urinary tract, Proteus mirabilis. We found that P. mirabilis can utilize chondroitin sulfate as a carbon source, and that chondroitin sulfate degradation contributes to infection in a model of catheterized urinary tract infection. This work contributes to a growing understanding of how uropathogens subvert host defenses and acquire nutrients within the bladder.

DOI: https://doi.org/10.64898/2026.03.02.708568
Carbohydr Polym. 2026 May 15. pii: S0144-8617(26)00165-7. [Epub ahead of print]380 125049

Degradation and utilization of chondroitin sulfate with different molecular weights by the gut microbiota from four midlife women: Role of Bacteroides ovatus AP1.

Junpeng Huang, Xinmiao Ren, Yaxue Liu, Mengshi Xiao, Yuhong Gao, Wen-Can Huang, Haijin Mou, Changliang Zhu.

  Chondroitin sulfate (CS) is a glycosaminoglycan that plays essential roles in physiological functions. However, the relationship between CS and the intestines of midlife women remains unclear. This study investigated the degradation and utilization of low-molecular-weight CS (LMWCS) and high-molecular-weight CS (HMWCS) using an invitro fermentation model with fecal samples from four midlife women. The result showed that 51% of LMWCS and 41% of HMWCS were degraded within 48 h, with interindividual variation. Both CS forms were ultimately degraded to an unsaturated disaccharide (udp2), while LMWCS was metabolized more efficiently. This result in higher production of short-chain fatty acids, particularly acetate and propionate. Fermentation of both CS forms increased Bacteroides abundance, with LMWCS more effectively promoting beneficial bacteria and reducing Klebsiella. Bacteroides ovatus AP1 was identified as a key CS-degrading species, efficiently utilizing both LMWCS (87%) and HMWCS (58%), producing udp2 and propionate. Whole-genome sequencing of B. ovatus AP1 revealed 649 carbohydrate-active enzyme genes, including multiple polysaccharide lyases involved in CS depolymerization. qPCR confirmed the upregulation of CS-metabolism-related genes during fermentation. These findings highlight the potential of LMWCS as a prebiotic for modulating gut microbiota and provide insights into the metabolism of CS by the gut microbiota.

Keywords:  Bacteroides ovatus; Chondroitin sulfate; Gut microbiota; In vitro fermentation; Midlife women; Molecular

DOI:  https://doi.org/10.1016/j.carbpol.2026.125049
Mol Cell Proteomics. 2026 Mar 12. pii: S1535-9476(26)00049-6. [Epub ahead of print] 101553

Glycoinformatic profiling of label-free intact heparan sulfate oligosaccharides.

Marissa L Maciej-Hulme, Jandi Kim, Elijah T Roberts, Yiqing Zhang, Anouk van der Velden, Dirk den Braanker, Cansu Yanginlar, Mark de Graaf, Ton Rabelink, Bernard van den Berg, Ellen van Omen, Rutger Maas, Anne-Els van de Logt, I Jonathan Amster, Johan van der Vlag.

  Heparan sulfates (HS) are a group of heterogenous linear, sulfated polysaccharides that play a role in in health and many diseases including cancer, cardiovascular, and kidney diseases. The structural variety of HS has greatly challenged the development and utility of HS analytics, particularly for native (non-depolymerized) structures, leaving a significant gap in HS technologies for clinical application. Mass spectrometry (MS)-based profiling with bioinformatics offers a top-down approach that can retain variety in large data sets. Using healthy human plasmas, we developed an MS glycoprofiling approach for native HS oligosaccharides, which retains the structural complexity of each individual HS chain and generates an HS 'index' (or Heparan-ome) for each patient. As a proof of concept, analysis of 53 plasma samples ranging from 4 groups of kidney disease patients revealed a new subset cluster (21%, 4/19) of membranous glomerulopathy (MG) patients with distinct HS profiles, highlighting the potential of HS glycoprofiling as a powerful new approach into clinical practice, which warrants future development into quantitative oliGAGomics and clinical diagnostics of kidney and other diseases.

Keywords:  glycomics; heparan sulfate; heparan sulfate profiling; kidney disease; mass spectrometry

DOI:  https://doi.org/10.1016/j.mcpro.2026.101553
Carbohydr Res. 2026 Mar 14. pii: S0008-6215(26)00078-9. [Epub ahead of print]564 109889

Controllable peroxidase-like catalysis of chondroitin sulfate-hemin conjugates for in situ hydrogel formation in biomedical applications.

Phuong Le Thi, Ngoc Quyen Tran, Anh Quan Hoang, Bich-Ngoc Chu, Duy-Tien Le, Dinh-Chuong Pham, Thanh Phu Nguyen, Dinh Trung Nguyen, Van Toan Nguyen.

  Chondroitin sulfate (CS)-based nanozymes have emerged as promising alternatives to natural enzymes for catalytic biomaterial fabrication. In this work, a hemin-functionalized chondroitin sulfate conjugate (CS-His-He) was developed as a peroxidase-mimicking catalyst for the oxidative crosslinking of tyramine-modified gelatin (Gel-Tyr), enabling in situ hydrogel formation under physiologically relevant conditions. The CS-His-He nanozyme efficiently catalyzed phenolic coupling reactions in the presence of hydrogen peroxide, producing Gel-Tyr hydrogels with physicochemical properties comparable to those obtained using horseradish peroxidase (HRP). The resulting hydrogels exhibited rapid gelation, stable network formation, and good hydrolytic stability, retaining approximately 73-75 wt% of their initial mass after 48 h under enzyme-free conditions. In the presence of collagenase, both hydrogel systems underwent rapid enzymatic degradation, with residual masses of about 23-20 wt% after 48 h, confirming their enzyme-responsive degradability. Cytocompatibility studies using human dermal fibroblasts showed high cellular metabolic activity (>95%) and normal cell morphology. Overall, the CS-His-He nanozyme effectively replaces HRP for Gel-Tyr hydrogel formation while maintaining comparable physicochemical properties, enzymatic degradability, and cytocompatibility, highlighting its potential as a robust catalytic platform for injectable biomaterials and enzyme-responsive hydrogel systems.

Keywords:  Chondroitin sulfate; Gelatin hydrogel; Hemin; Horseradish peroxidase

DOI:  https://doi.org/10.1016/j.carres.2026.109889
ACS Omega. 2026 Mar 10. 11(9): 14719-14728

Inhibition of Dermatan Sulfate Epimerase 1 by Substituted Glucuronic Acids.

Roberto Mastio, Isolde Zuleta Sjögren, John Dahlquist, Anders Sundin, Gunilla Westergren-Thorsson, Sophie Manner, Emil Tykesson, Anders Malmström, Ulf Ellervik.

Dermatan sulfate epimerase 1 (DS-epi1) is a key enzyme in the biosynthesis of the glycosaminoglycan chondroitin sulfate/dermatan sulfate, catalyzing the conversion of glucuronic acid to iduronic acid at the polymer level. Chondroitin sulfate/dermatan sulfate chains are found on at least 32 proteoglycans, many of which are implicated in human diseases and syndromes, as well as in both malignant and normal cell development. DS-epi1 therefore represents a promising target for drug development, and recent structural studies have provided insights into its active site and catalytic mechanism. Here, we report the synthesis and biological evaluation of inhibitors based on 1,4-disubstituted glucuronic acids. These compounds were synthesized from glucose through a divergent approach, yielding 19 derivatives that were tested in a functional assay. To explore the importance of the carboxylic acid moiety, we also tested the methyl ester analog and the analogous xylose derivative. The most potent compound exhibited an IC50 of 42 ± 4 μM. Molecular dynamics simulations showed a strong interaction with the active site of DS-epi1.

DOI: https://doi.org/10.1021/acsomega.5c10686
Transpl Int. 2026 ;39 15502

Effect of Normothermic Machine Perfusion on Glycocalyx Shedding During Liver Transplantation - A Prospective Pilot Study.

Simon Mathis, Gabriel Putzer, Lukas Gasteiger, Nikolai Staier, Lisa Schlosser, Pia Tscholl, Robert Breitkopf, Benno Cardini, Alexander Kofler, Rupert Oberhuber, Thomas Resch, Stefan Schneeberger, Judith Martini.

  Ischemia-reperfusion injury (IRI) plays a pivotal role in liver transplantation by inducing oxidative stress and inflammation, thereby contributing to impaired graft function and postoperative complications. A key element of IRI is degradation of the endothelial glycocalyx, resulting in microcirculatory dysfunction. This study investigated the impact of normothermic machine perfusion (NMP) on glycocalyx integrity and its association with early postoperative outcomes. Thirty grafts undergoing NMP prior to transplantation were analyzed. Syndecan-1 and heparan sulfate were quantified in perfusate and recipient serum. Donor-related factors influencing glycocalyx injury during NMP were assessed, and correlations with outcomes established. Syndecan-1 levels increased during NMP and remained significantly elevated in grafts from circulatory-death (DCD) donors compared with brain-death (DBD) donors. Receiver operating characteristics revealed predictive potential for early allograft dysfunction (EAD) with a syndecan-1 cut-off of 4,796.13 ng/mL after 6 h of NMP. In contrast, heparan sulfate concentrations showed no relevant changes. Postoperatively, syndecan-1 levels in recipient serum were elevated immediately after transplantation but declined over subsequent days, while heparan sulfate remained stable. These findings indicate that glycocalyx injury develops during NMP, particularly in DCD livers, with elevated syndecan-1 reflecting endothelial vulnerability and a potentially modifiable aspect of graft physiology relevant to future protective strategies.
Clinical Trial Registration: www.Clinicaltrials.gov, identifier NCT: 04764266.

Keywords:  glycocalyx; heparan sulfate; liver transplantation; normothermic machine perfusion; syndecan-1

DOI:  https://doi.org/10.3389/ti.2026.15502
Science. 2026 Mar 19. 391(6791): 1250-1255

Host-derived nitrate fuels indole production by Escherichia coli to drive chronic kidney disease progression.

Jee-Yon Lee, Scott P Mahan, Thaynara Parente de Carvalho, Henry Nguyen, Chonikarn Singai, Lizbeth Camacho, Mert Tekeli, Yu-Jin Kwon, Ji-Won Lee, Renato L Santos, Renée M Tsolis, Sebastian E Winter, Andreas J Bäumler.

Chronic kidney disease (CKD) is linked to an elevated fecal abundance of Enterobacteriaceae, but the ecological drivers of this shift and its impact on disease progression remain unclear. The uremic toxin indoxyl sulfate is produced from microbiota-derived indole in the liver. Here, we found that in mice with adenine-induced CKD, impaired clearance of indoxyl sulfate elevated mucosal expression of the gene encoding inducible nitric oxide synthase (iNOS). The resulting rise in luminal nitrate levels promoted Escherichia coli growth by means of nitrate respiration. Fecal microbiota from CKD patients generated more indole than feces of healthy controls during anaerobic culture, but only in the presence of nitrate. Nitrate enhanced indole production by E. coli, thereby worsening renal pathology in CKD mice, which was mitigated by iNOS inhibition.

DOI: https://doi.org/10.1126/science.ady5217
F1000Res. 2025 ;14 1323

Sulfated Exopolysaccharides from Porphyridium purpureum: A Review of Extraction, Structural Characterization, and Chemical Properties for Advanced Applications.

Devi Maulina, Abdul Mun'im, Asep Bayu, Heri Setiawan, Najihah Mohd Hashim.

  Microalgae are increasingly recognized as sustainable green cell factories capable of producing a various high-value bioactive compounds. Among them, the red microalga Porphyridium purpureum stands out for its unique ability to secrete sulfated exopolysaccharides (sEPS)-complex macromolecules enriched with sulfate and uronic acid groups that exhibit potent biological activities. These compounds function as natural antioxidants, immunomodulators, and antimicrobial agents, attracting substantial interest from the pharmaceutical, cosmetics, and functional food industries. A targeted literature search was conducted across the Scopus, PubMed, Web of Science and ScienceDirect databases to identify studies focusing on the extraction, structural characterization, and applications of sulfated exopolysaccharides from Porphyridium purpureum between 2015 and 2025. Recent research has demonstrated rapid advancements in environmentally friendly extraction technologies, including membrane filtration, three-phase partitioning (TPP), ultrasound-assisted TPP (UATPP), and deep eutectic solvents (DES), which collectively enhance the yield, purity, and preserve the biological functionality of sEPS. Furthermore, significant progress has been made in structural and mechanistic elucidation through advanced analytical and imaging techniques such as two-dimensional NMR spectroscopy, FTIR, methylation analysis, and transcriptomic profiling. These approaches have clarified how cultivation parameters and environmental stressors influence EPS biosynthesis, sulfation patterns, and biological activity. Overall, this review provides an integrated and forward-looking perspective on the scientific advances and technological challenges surrounding P. purpureum sEPS, outlining future directions toward sustainable bioprocessing and industrial valorization of these high-value biomacromolecules.

Keywords:  Porphyridium purpureum; sulfated exopolysaccharides; green extraction; membrane technology; structural characterization; bioactivity.

DOI:  https://doi.org/10.12688/f1000research.173006.2
Carbohydr Polym. 2026 May 15. pii: S0144-8617(26)00250-X. [Epub ahead of print]380 125134

Advances in fucoidan extraction and structure-bioactivity relationships.

Emmanuel Ofosu Mensah, Jens Sommer-Knudsen, Morten Thaysen-Andersen, Anwar Sunna.

  Fucoidan is a sulfated polysaccharide from brown seaweeds whose heterogeneous structure and broad bioactivities have stimulated extensive investigation. While primarily composed of fucose, its composition varies in monosaccharide content (e.g. galactose, xylose, mannose, glucuronic acid), backbone architecture, branching, and sulfation patterns, with these features influenced by species, environmental factors, and extraction conditions. Because extraction methods can preserve or degrade structural motifs essential to bioactivity, methodological variation has contributed to longstanding inconsistencies in reported structure-bioactivity relationships. This review critically explores advances in fucoidan extraction, including emerging optimization strategies and sequential extraction approaches, and evaluates their effects on yield, purity, and structural integrity. We further examine recent developments in understanding structure-bioactivity relationships, highlighting insights derived from molecular docking, multi-omics platforms, and integrative systems-level analyses. Together, these perspectives provide a consolidated framework for relating extraction conditions, structural characteristics, and biological function in fucoidan research.

Keywords:  Bioactivity; Extraction; Fucoidan; Purification; Structure; Sulfation

DOI:  https://doi.org/10.1016/j.carbpol.2026.125134
Cell Rep Med. 2026 Mar 17. pii: S2666-3791(26)00101-1. [Epub ahead of print]7(3): 102684

Neuroprotective response against the onset of ischemic stroke by upregulation of histone H3Y99 sulfation.

Li Jiang, Junchang Xie, Jianfeng Wang, Yili Yi, Runxin Zhou, Dingyuan Guo, Yu Wang, Xiao Zeng, Mingxuan Shi, Jianing Ding, Jiadi Wu, Jun Zhao, Siyu Feng, Nan Wang, Qian Shen, Yuping Yin, Mingchang Li, Yugang Wang.

  Protective cerebral responses against stresses are fundamental quests of medical science. Here, we report that upregulation of histone sulfation is a protective cerebral response against ischemic injury. Ischemia upregulates the SLC26A1-PAPSS1-SULT1B1 axis, which mediates the transportation of sulfate into cells, conversion of sulfate into PAPS, and catalysis of histone sulfation (H3Y99sulf) using PAPS, respectively. Upregulated H3Y99sulf promotes metabolic genes transcription and glycolysis, sustaining cell survival in ischemic stress. In the mouse model of transient middle cerebral artery occlusion, both PAPSS1 overexpression and sulfate supplementation can boost the neuroprotective H3Y99sulf mechanism, reduce brain injury, and improve neurological functions; disruption of H3Y99sulf exacerbates ischemia-induced brain injury and counteracts the neuroprotective effect of sulfate. Ischemia patients with higher serum sulfate levels are prone to have smaller infarcts, alleviated severity assessments, and better clinical outcomes. This study unearths an undocumented protective cerebral response against ischemia that might be targeted for ischemic stroke treatment.

Keywords:  histone sulfation; ischemic stroke; neuroprotective response

DOI:  https://doi.org/10.1016/j.xcrm.2026.102684
J Genet Eng Biotechnol. 2026 Mar;pii: S1687-157X(25)00195-7. [Epub ahead of print]24(1): 100651

Integrative analysis of sulfate transporters in Citrus sinensis reveals CsSULTR3;5 involved in pathogen stress response.

Xinyou Wang, Xuetong Chen, Nannan Lu, Jiaoyan Zhong, Xinlv Dai, Xia Zhuang, Fengxian Yao, Ruimin Li.

  Selenium treatment has been shown to enhance plant resilience against both biotic and abiotic stresses; however, whether it can improve citrus resistance to bacterial diseases remains unexplored. In this study, we systematically identified sulfate transporter (Sultr) genes in the Citrus sinensis genome that are involved in selenate uptake. Analysis of gene structure, conserved motifs, and protein domains revealed a high degree of conservation among CsSultrs. Collinearity analysis between C. sinensis and Arabidopsis thaliana Sultr genes suggested possible evolutionary duplication and divergence events. Expression profiling of sulfur-related genes in C. sinensis following infection with Candidatus Liberibacter asiaticus, Xanthomonas citri subsp. citri, and Colletotrichum gloeosporioides showed that CsSULTR3;5 is responsive to pathogen infection. Subcellular localization indicated that CsSULTR3;5 is localized to the cell membrane and other intracellular organelles. Transient expression of CsSULTR3;5 in Nicotiana benthamiana did not affect leaf chlorophyll or carotenoid content. Furthermore, overexpression of CsSULTR3;5 enhanced resistance to citrus canker. These findings provide insight into the mechanisms by which selenium modulates biotic stress responses in citrus.

Keywords:  Citrus sinensis; Pathogen; Response; Selenium; Sulfate transporter

DOI:  https://doi.org/10.1016/j.jgeb.2025.100651