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Updated: Jan 17, 2026
High-throughput Assay to Phenotype Salmonella enterica Typhimurium Association, Invasion, and Replication in Macrophages
Published on: August 11, 2014
Mucus-derived glycans are inhibitory signals for Salmonella Typhimurium SPI-1-mediated invasion
Kelsey M Wheeler1, Michaela A Gold2, Corey A Stevens1
1Biological Engineering Department, Massachusetts Institute of Technology, Cambridge, MA, USA.
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.
Insights
Intestinal mucins inhibit Salmonella invasion by suppressing the HilD virulence regulator. Specific mucin sugars, N-acetyl galactosamine and N-acetyl glucosamine, mediate this anti-virulence effect, offering potential for new infection treatments.
Area of Science:
- Microbiology
- Immunology
- Glycobiology
Background:
- Mucus acts as a barrier against enteric pathogens like Salmonella Typhimurium.
- Core 3 glycosylation of mucins is protective, but mechanisms are unknown.
Purpose of the Study:
- Elucidate the molecular mechanisms of mucin's protective effect against S. Typhimurium.
- Identify specific mucin components responsible for anti-virulence activity.
Main Methods:
- Investigated the effect of native intestinal mucins on Salmonella invasion of colonic epithelial cells.
- Analyzed the role of mucin glycans and specific sugars in inhibiting the type 3 secretion system (T3SS) and HilD.
- Examined the interaction between mucin sugars and HilD's putative carbohydrate-binding domain.
Main Results:
- Native intestinal mucins inhibit Salmonella invasion by downregulating the T3SS.
- Mucin glycans, specifically N-acetyl galactosamine and N-acetyl glucosamine, are responsible for the anti-virulence effect.
- The native presentation of these sugars is crucial for their activity, likely through interaction with HilD.
Conclusions:
- Mucins' anti-virulence effect is mediated by specific sugars that suppress the key virulence regulator HilD.
- Mucin-based strategies show promise for combating enteric infections.
- Mucins may act as broad-spectrum anti-virulence agents against pathogens with similar regulators.
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