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Mucin dynamics in intestinal bacterial infection.

Lindén SK, Florin TH, McGuckin MA - PLoS ONE (2008)

Bottom Line: C. rodentium bound to the major secreted mucin, Muc2, in vitro, and high numbers of bacteria were found in secreted MUC2 in infected animals in vivo, indicating that mucins may limit bacterial access to the epithelial surface.In the small intestine, caecum and proximal colon, the mucin expression was similar in infected and non-infected animals.Major changes in both the cell-surface and secreted mucins occur in response to intestinal infection.

View Article: PubMed Central - PubMed

Affiliation: Mucosal Diseases Program, Mater Medical Research Institute, Mater Health Services, South Brisbane, Queensland, Australia.

ABSTRACT

Background: Bacterial gastroenteritis causes morbidity and mortality in humans worldwide. Murine Citrobacter rodentium infection is a model for gastroenteritis caused by the human pathogens enteropathogenic Escherichia coli and enterohaemorrhagic E. coli. Mucin glycoproteins are the main component of the first barrier that bacteria encounter in the intestinal tract.

Methodology/principal findings: Using Immunohistochemistry, we investigated intestinal expression of mucins (Alcian blue/PAS, Muc1, Muc2, Muc4, Muc5AC, Muc13 and Muc3/17) in healthy and C. rodentium infected mice. The majority of the C. rodentium infected mice developed systemic infection and colitis in the mid and distal colon by day 12. C. rodentium bound to the major secreted mucin, Muc2, in vitro, and high numbers of bacteria were found in secreted MUC2 in infected animals in vivo, indicating that mucins may limit bacterial access to the epithelial surface. In the small intestine, caecum and proximal colon, the mucin expression was similar in infected and non-infected animals. In the distal colonic epithelium, all secreted and cell surface mucins decreased with the exception of the Muc1 cell surface mucin which increased after infection (p<0.05). Similarly, during human infection Salmonella St Paul, Campylobacter jejuni and Clostridium difficile induced MUC1 in the colon.

Conclusion: Major changes in both the cell-surface and secreted mucins occur in response to intestinal infection.

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Related in: MedlinePlus

C. rodentium binding to Muc2.ELISA plates were coated with the “insoluble” Muc2 complex or with BSA and incubated with biotinylated C. rodentium. Statistics: Mean±SD, *** p<0.001 (t-test, n = 6) (A). Large amounts of bacteria can be found entangled in the secreted Muc2 in C. rodentium infected animals (B–D). By brightfield observation using a 20× lens (B) the Muc2 is visualized as a brown stain, and the presence of large amounts of bacteria within the secreted Muc2 can be seen by reflected light Nomarski differential interference observation (C; 40× lens and D; 100× lens).
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pone-0003952-g007: C. rodentium binding to Muc2.ELISA plates were coated with the “insoluble” Muc2 complex or with BSA and incubated with biotinylated C. rodentium. Statistics: Mean±SD, *** p<0.001 (t-test, n = 6) (A). Large amounts of bacteria can be found entangled in the secreted Muc2 in C. rodentium infected animals (B–D). By brightfield observation using a 20× lens (B) the Muc2 is visualized as a brown stain, and the presence of large amounts of bacteria within the secreted Muc2 can be seen by reflected light Nomarski differential interference observation (C; 40× lens and D; 100× lens).

Mentions: In the healthy intestine, Muc2 is the main secreted mucin composing the mucus layer, which is continuously washing the intestinal surface to clear trapped material. Using a microtiter based assay, we demonstrated that murine Muc2 can bind to C. rodentium (Figure 7A). Although it cannot be excluded that the insoluble Muc2 complex used in this study could contain small amounts of contamination with other reduction sensitive polymeric complexes (for example other mucins), large amounts of bacteria were found in the secreted Muc2 in C. rodentium infected animals (Figure 7B–D), consistent with Muc2 binding to C. rodentium.


Mucin dynamics in intestinal bacterial infection.

Lindén SK, Florin TH, McGuckin MA - PLoS ONE (2008)

C. rodentium binding to Muc2.ELISA plates were coated with the “insoluble” Muc2 complex or with BSA and incubated with biotinylated C. rodentium. Statistics: Mean±SD, *** p<0.001 (t-test, n = 6) (A). Large amounts of bacteria can be found entangled in the secreted Muc2 in C. rodentium infected animals (B–D). By brightfield observation using a 20× lens (B) the Muc2 is visualized as a brown stain, and the presence of large amounts of bacteria within the secreted Muc2 can be seen by reflected light Nomarski differential interference observation (C; 40× lens and D; 100× lens).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2601037&req=5

pone-0003952-g007: C. rodentium binding to Muc2.ELISA plates were coated with the “insoluble” Muc2 complex or with BSA and incubated with biotinylated C. rodentium. Statistics: Mean±SD, *** p<0.001 (t-test, n = 6) (A). Large amounts of bacteria can be found entangled in the secreted Muc2 in C. rodentium infected animals (B–D). By brightfield observation using a 20× lens (B) the Muc2 is visualized as a brown stain, and the presence of large amounts of bacteria within the secreted Muc2 can be seen by reflected light Nomarski differential interference observation (C; 40× lens and D; 100× lens).
Mentions: In the healthy intestine, Muc2 is the main secreted mucin composing the mucus layer, which is continuously washing the intestinal surface to clear trapped material. Using a microtiter based assay, we demonstrated that murine Muc2 can bind to C. rodentium (Figure 7A). Although it cannot be excluded that the insoluble Muc2 complex used in this study could contain small amounts of contamination with other reduction sensitive polymeric complexes (for example other mucins), large amounts of bacteria were found in the secreted Muc2 in C. rodentium infected animals (Figure 7B–D), consistent with Muc2 binding to C. rodentium.

Bottom Line: C. rodentium bound to the major secreted mucin, Muc2, in vitro, and high numbers of bacteria were found in secreted MUC2 in infected animals in vivo, indicating that mucins may limit bacterial access to the epithelial surface.In the small intestine, caecum and proximal colon, the mucin expression was similar in infected and non-infected animals.Major changes in both the cell-surface and secreted mucins occur in response to intestinal infection.

View Article: PubMed Central - PubMed

Affiliation: Mucosal Diseases Program, Mater Medical Research Institute, Mater Health Services, South Brisbane, Queensland, Australia.

ABSTRACT

Background: Bacterial gastroenteritis causes morbidity and mortality in humans worldwide. Murine Citrobacter rodentium infection is a model for gastroenteritis caused by the human pathogens enteropathogenic Escherichia coli and enterohaemorrhagic E. coli. Mucin glycoproteins are the main component of the first barrier that bacteria encounter in the intestinal tract.

Methodology/principal findings: Using Immunohistochemistry, we investigated intestinal expression of mucins (Alcian blue/PAS, Muc1, Muc2, Muc4, Muc5AC, Muc13 and Muc3/17) in healthy and C. rodentium infected mice. The majority of the C. rodentium infected mice developed systemic infection and colitis in the mid and distal colon by day 12. C. rodentium bound to the major secreted mucin, Muc2, in vitro, and high numbers of bacteria were found in secreted MUC2 in infected animals in vivo, indicating that mucins may limit bacterial access to the epithelial surface. In the small intestine, caecum and proximal colon, the mucin expression was similar in infected and non-infected animals. In the distal colonic epithelium, all secreted and cell surface mucins decreased with the exception of the Muc1 cell surface mucin which increased after infection (p<0.05). Similarly, during human infection Salmonella St Paul, Campylobacter jejuni and Clostridium difficile induced MUC1 in the colon.

Conclusion: Major changes in both the cell-surface and secreted mucins occur in response to intestinal infection.

Show MeSH
Related in: MedlinePlus