Mucus-derived glycans are inhibitory signals for Salmonella Typhimurium SPI-1-mediated invasion
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PIIS2211124725010757.pdf
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6.62 MB
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Author(s)
Wheeler, Kelsey M.
Gold, Michaela A.
Stevens, Corey A.
Tedin, Karsten
Wood, Amanda M.
Uzun, Deniz
Cárcamo-Oyarce, Gerardo
Turner, Bradley S.
Fulde, Marcus
Song, Jeongmin
Date Issued
September 23, 2025
Journal
Cell Reports
Publisher
Elsevier BV
Citation
Mucus-derived glycans are inhibitory signals for Salmonella Typhimurium SPI-1-mediated invasion. Wheeler, Kelsey M. et al. Cell Reports, 116304.
Version
Final published version
Abstract
Mucus forms a critical barrier against enteric pathogens like Salmonella enterica serovar Typhimurium. While in vivo studies indicate that secreted, gel-forming mucins and specifically core 3 glycosylation are protective against S. Typhimurium, the molecular mechanisms involved remain unclear. Here, we demonstrate that native intestinal mucins inhibit Salmonella invasion of colonic epithelial cells by downregulating the type 3 secretion system through suppression of the key virulence regulator, HilD. Our study identifies mucin glycans and specific mucin sugars, namely N-acetyl galactosamine and N-acetyl glucosamine, as the components responsible for mucin’s anti-virulence effect, likely via functional or direct interaction with HilD’s putative carbohydrate-binding domain. Notably, we find that the native presentation of these sugars is important for activity. These insights provide a mechanistic foundation for mucin-based strategies to combat enteric infections and, given the prevalence of homologous AraC-type regulators in other pathogens, suggest mucins’ potential as broad-spectrum anti-virulence agents.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Microbiology Graduate Program
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Creative Commons Attribution
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DOI of Published Version
https://doi.org/10.1016/j.celrep.2025.116304
