Biology subjects

Fentker, K.

Publications and source records attributed to Fentker, K..

3 recordsLinked to original sources

bioRxiv2024

Structural Determinants of Mucins in Influenza Virus Inhibition: The Synergistic Role of Sialylated Glycans and Molecular Size

Mucins are heavily glycosylated proteins that play a crucial role in protecting mucosal surfaces against pathogens, including influenza viruses. This study investigates the antiviral properties of bovine submaxillary mucins (BSM) as a model for oral mucins against the influenza virus (A/H3N2 subtype), focusing on glycan composition and mucin size. BSM was purified, and characterized by proteomic and glycomic analysis and its antiviral efficacy was assessed after selective removal of sialic acids, N-glycans, or all glycans via enzymatic and chemical treatments. We employed virus binding and inhibition assays, including microscale thermophoresis (MST) and hemagglutination inhibition (HAI), to characterize processed mucins for structure activity correlations. Removal of sialic acids reduced BSMs antiviral activity by over 10-fold, while complete glycan removal abolished it entirely, highlighting sialylated O-glycans as critical for viral inhibition. N-glycan removal had minimal impact on antiviral efficacy. A size-dependent antiviral effect was observed: smaller mucin fragments ([~]50 and 330 kDa), which retained comparable O-glycosylation patterns, showed significantly reduced inhibition and viral binding affinity compared to intact BSM. These findings underscore the importance of mucin size and sialylated O-glycans in antiviral defense mechanisms against influenza. SignificanceThis study sheds light on the intrinsic antiviral properties of mucin from the bovine submaxillary gland, revealing the roles of glycans and mucins size in binding and inhibiting influenza virus. Our findings suggest a clear correlation between sialylated O-glycans and mucin size with the antiviral efficacy. Ultimately, we show that mucin-derived fragments retaining virus-binding capacity, with defined size and O-glycosylation patterns, can be isolated from mucin and could serve as versatile building blocks for designing next-generation antiviral biomaterials.

biochemistry↗

bioRxiv2024

Systemic effects of cystic fibrosis transmembrane conductance regulator (CFTR) modulators on the blood proteome

Cystic fibrosis (CF), resulting from a dysfunction in the cystic fibrosis transmembrane conductance regulator (CFTR), affects multiple organs through mucus obstruction and differences in secretion. The CFTR modulator drug combination elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA, ETI) has markedly improved clinical symptoms, but its broader molecular and systemic effects remain to be fully elucidated. We employed mass spectrometry-based proteomics to compare the blood proteomes of CF patients treated with the earlier, less effective lumacaftor/ivacaftor (LUM/IVA) combination against those receiving the more potent ELX/TEZ/IVA therapy. Our analysis revealed both specific and common pharmacodynamic signatures associated with inflammation and metabolic processes under each treatment regimen. Notably, ELX/TEZ/IVA therapy exhibited more consistent alterations across patients that were directed towards profiles observed in healthy individuals. Furthermore, by comparing sputum and blood proteomes of ELX/TEZ/IVA treated patients we identified counter-directional changes in the pulmonary surfactant-associated protein B, SFTPB, a potential biomarker of lung tissue repair, which also correlated with lung function improvements. This study provides a comprehensive resource that enhances our understanding of CFTR modulator-driven proteome alterations, offering insights to both systemic and local protein regulation in CF. Our findings indicate that ELX/TEZ/IVA promotes broader systemic health improvements, providing critical insights that could shape future therapeutic strategies in CF.

molecular biology↗

bioRxiv2024

A comprehensive characterization of the viscoelastic properties of Bovine Submaxillary Mucin (BSM) and the effect of additives

This study presents a comprehensive characterization of the viscoelastic and structural properties of Bovine Submaxillary Mucin (BSM), which is widely used as a commercial source to conduct mucus-related research. We conducted concentration studies of BSM and examined the effects of various additives - NaCl, CaCl2, lysozyme, and DNA - on its rheological behavior. A notable connection between BSM concentration and viscoelastic properties was observed, particularly under varying ionic conditions. The rheological spectra could be well-described by a fractional Kelvin-Voigt Model with a minimum of model parameters. A detailed proteomics analysis provided insight into the molecular interactions within BSM, showing MUC19 as main component. Cryo-scanning electron microscopy allowed to visualize the network structure in relation to the rheological data. By elucidating the complex interplay between mucin concentration, environmental conditions, and viscoelastic properties, this research significantly contributes to the field of mucus research and lays an important basis for its further advancement.

biophysics↗