The colonic epithelial surface is protected by an inner mucus layer that the commensal microflora cannot penetrate. We previously demonstrated that Entamoeba histolytica secretes a protease capable of dissolving this layer that is required for parasite penetration. Here, we asked whether there are bacteria that can secrete similar proteases. We screened bacterial culture supernatants for such activity using recombinant fragments of the MUC2 mucin, the major structural component, and the only gel-forming mucin in the colonic mucus. MUC2 has two central heavily O-glycosylated mucin domains that are protease-resistant and has cysteine-rich N and C termini responsible for polymerization. Culture supernatants of Porphyromonas gingivalis, a bacterium that secretes proteases responsible for periodontitis, cleaved the MUC2 C-terminal region, whereas the N-terminal region was unaffected. The active enzyme was isolated and identified as Arg-gingipain B (RgpB). Two cleavage sites were localized to IR↓TT and NR↓QA. IR↓TT cleavage will disrupt the MUC2 polymers. Because this site has two potential O-glycosylation sites, we tested whether recombinant GalNAc-transferases (GalNAc-Ts) could glycosylate a synthetic peptide covering the IRTT sequence. Only GalNAc-T3 was able to glycosylate the second Thr in IRTT, rendering the sequence resistant to cleavage by RgpB. Furthermore, when GalNAc-T3 was expressed in CHO cells expressing the MUC2 C terminus, the second threonine was glycosylated, and the protein became resistant to RgpB cleavage. These findings suggest that bacteria can produce proteases capable of dissolving the inner protective mucus layer by specific cleavages in the MUC2 mucin and that this cleavage can be modulated by site-specific O-glycosylation.
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http://dx.doi.org/10.1074/jbc.M113.459479 | DOI Listing |
Int J Mol Sci
January 2025
College of Animal Science and Technology, Northeast Agricultural University, No. 600 Changjiang Road, Xiangfang District, Harbin 150030, China.
To explore the relationship between intestinal mucin 2 () and weaning-induced diarrhoea in piglets, we analysed and piglets. The piglets were divided into a healthy weaned group, a weaned diarrhoea group, and a healthy unweaned control group. Intestinal tissues were collected, and goblet cell numbers, sizes, and degrees of intestinal injury were observed and recorded.
View Article and Find Full Text PDFPoult Sci
January 2025
Laboratory of Animal Nutrition, Department of Animal Science, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan. Electronic address:
Paddy rice ingestion increases intestinal mucin secretion and production by enhancing MUC2 gene expression and epithelial turnover. In this study, we performed a comprehensive analysis of intestinal gene expression in chickens fed paddy rice and investigated whether the intestinal IgA response was modified by paddy rice ingestion. Furthermore, we investigated the possible involvement of gut fermentation.
View Article and Find Full Text PDFFront Pharmacol
January 2025
School of Pharmacy, Xinjiang Medical University, Urumchi, China.
Background: In the Kazakh community of Xinjiang, China, fermented camel milk has been traditionally used to manage diabetes. This study evaluates the effects of composite probiotics derived from fermented camel milk (CPCM) on metabolic disturbances in a rat model of Type 2 diabetes (T2DM).
Methods: T2DM was induced in Wistar rats using streptozotocin.
Vet Res
January 2025
Heilongjiang Provincial Key Laboratory of Zoonosis, College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
Trichinella spiralis (T. spiralis) is a highly pathogenic zoonotic nematode that poses significant public health risks and causes substantial economic losses. Understanding its invasion mechanisms is crucial.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Physical Engineering Faculty, Novosibirsk State Technical University, 630073 Novosibirsk, Russia.
In the development of inflammatory bowel disease (IBD), peritoneal macrophages contribute to the resident intestinal macrophage pool. Previous studies have demonstrated that oral administration of L-fucose exerts an immunomodulatory effect and repolarizes the peritoneal macrophages in vivo in mice. In this study, we analyzed the phenotype and metabolic profile of the peritoneal macrophages from mice, as well as the effect of L-fucose on the metabolic and morphological characteristics of these macrophages in vitro.
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