Discovery of a secreted Bacteroides fragilis mucinase that cleaves mucins with bis-T O-glycans through a carbohydrate binding module-dependent mechanism
Issued Date
2026-01-01
Resource Type
ISSN
19490976
eISSN
19490984
Scopus ID
2-s2.0-105033395529
Journal Title
Gut Microbes
Volume
18
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
Gut Microbes Vol.18 No.1 (2026)
Suggested Citation
Narimatsu Y., Pleguezuelos-Manzano C., Hornikx D., Goerdeler F., Jaroentomeechai T., Flores K., Narimatsu S., Boot C., Hansen L., Durbesson F., Vincentelli R., Comstock L., Clevers H., Taleb V., Corzana F., Henrissat B., Clausen H., Hurtado-Guerrero R., Büll C. Discovery of a secreted Bacteroides fragilis mucinase that cleaves mucins with bis-T O-glycans through a carbohydrate binding module-dependent mechanism. Gut Microbes Vol.18 No.1 (2026). doi:10.1080/19490976.2026.2644983 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/115877
Title
Discovery of a secreted Bacteroides fragilis mucinase that cleaves mucins with bis-T O-glycans through a carbohydrate binding module-dependent mechanism
Author's Affiliation
The University of Chicago
Technical University of Denmark
Radboud Universiteit
Universidad de Zaragoza
Det Sundhedsvidenskabelige Fakultet
Faculty of Science, Mahidol University
Universidad de La Rioja
Hubrecht Institute for Developmental Biology and Stem Cell Research - KNAW
Fundación Agencia Aragonesa para la Investigación y el Desarrollo (ARAID)
Laboratoire Architecture et Fonction des Macromolécules Biologiques
GlycoDisplay ApS
Technical University of Denmark
Radboud Universiteit
Universidad de Zaragoza
Det Sundhedsvidenskabelige Fakultet
Faculty of Science, Mahidol University
Universidad de La Rioja
Hubrecht Institute for Developmental Biology and Stem Cell Research - KNAW
Fundación Agencia Aragonesa para la Investigación y el Desarrollo (ARAID)
Laboratoire Architecture et Fonction des Macromolécules Biologiques
GlycoDisplay ApS
Corresponding Author(s)
Other Contributor(s)
Abstract
Degradation of mucins at the host–microbial mucus interphase involves glycosidases that release monosaccharides from O-glycans and mucinases that cleave the mucin protein backbone. Mucinases recognize and cleave peptide bonds at specific sequence motifs with varying O-glycan structures required and/or permissible. Mucinases that digest mucins with intact O-glycans can potentially destroy the protective mucus, while mucinases that only digest mucins with partially degraded O-glycans may serve at a later stage of nutrient sourcing from mucins. Here, we discovered nine CBM-bearing M60-like mucinases across gut commensals and opportunists, including a conserved Bacteroides fragilis mucinase denoted HC11. We also investigated the previously described Bacteroides thetaiotaomicron mucinase BT4244, which together delineates two functional classes with distinct preferences: BT4244 for bis-Tn (GalNAcα1-O-Ser/Thr) and HC11 for bis-T (Galβ1-3GalNAcα1-O-Ser/Thr) O-glycans. Both mucinases harbor carbohydrate-binding modules (CBM32) that bind their cognate O-glycan motifs and are required–together with the catalytic domains–for efficient cleavage of extended mucin domains, which is consistent with cooperative engagement, but are not required for the cleavage of short glycopeptides. We show B. fragilis strains secrete HC11 and degrade mucins only after the removal of sialic acids. Together, these findings expand the mucinase repertoire by nine enzymes spanning commensals and opportunists, demonstrate that CBM32 domains are essential for efficient cleavage of extended mucin substrates likely by promoting multivalent engagement and substrate positioning, and nominateidentify CBM–catalytic cooperation as a mechanism and intervention point for controlling mucus turnover and barrier integrity.