{"doi":"10.24834/isbn.9789178776429","title":"Breaking the Barrier – Insights into Mucin-Degrading Proteases in Oral Bacteria","abstract":"Mucins are large, glycosylated proteins that form the structural backbone of mucus and play a central role in shaping microbial communities at mucosal surfaces. In the oral cavity, the predominant salivary mucin MUC5B provides structural support for biofilm formation and mediates host-microbe interactions. Deciphering how MUC5B is modulated by microbial effector molecules is key to understand how biofilms are formed, developed and reorganized. This thesis investigates three previously uncharacterized mucin-degrading proteases — MdpL from Limosilactobacillus fermentum, and MdpS and MdpS2 from Streptococcus oralis. Using a multidisciplinary approach, this work demonstrates that the enzymes extensively degrade MUC5B in a domain-specific and functionally significant manner. Each enzyme displayed distinct physicochemical traits and substrate preferences, reflecting their ecological adaptation to different biofilm niches and highlighting the evolutionary diversity of mucin-degrading strategies. The findings contribute to oral microbiology by linking specific enzymatic activities to MUC5B network remodeling, and biofilm dispersal. In enzymology, they introduce a novel class of mucin-targeting proteases with non-canonical activation, regulation, and substrate recognition. From a mucin biology perspective, this work challenges the glycosidase-centric model of mucin degradation and demonstrates that domain-specific proteolysis can initiate structural remodeling and changes in the physical properties of mucins. Together, these insights reveal mucin-degrading proteases as active agents of ecological change at the host-biofilm interface and open new avenues for targeted modulation of mucus environments. The work also lays a foundation for future studies in microbial ecology, the discovery of additional Mdp-like enzymes, and a broader exploration of enzyme-driven mechanisms in biofilm development.","journal":"KTH Publication Database DiVA (KTH Royal Institute of Technology)","year":2025,"id":579938,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9492,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1489374,"name":"Fredrik Leo","orcid":"0000-0003-1605-5201","position":0,"is_corresponding":true}],"reference_count":200,"raw_metadata":null,"created_at":"2026-07-19T02:58:34.718602Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}