Primary murine mucosal response during cephalosporin-induced intestinal colonization by Enterococcus faecium
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Published on: February 6, 2021
Antoni P A Hendrickx1, Denise van de Kamer1, Rob J L Willems1
1Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
Abstract:
Hospitalized patients are often administered antibiotics that perturb the gastrointestinal commensal microbiota, leading to outgrowth of antibiotic-resistant bacteria, like multidrug-resistant Enterococcus faecium, subsequent spread, and eventually infections. However, the events that occur at the initial stage of intestinal colonization and outgrowth by multidrug-resistant E. faecium within the antibiotic-treated host have not been thoroughly studied. Here, we describe and visualize that only 6 hr after cephalosporin treatment of mice, the Muc-2 mucus layer is reduced and E-cadherin junctions were altered. In contrast, the cadherin-17 junctions were unaffected in antibiotic treated mice during E. faecium colonization or in untreated animals. E. faecium was capable to colonize the mouse colon already within 6 hr after inoculation, and agglutinated at the apical side of the intestinal epithelium. During the primary stage of gastrointestinal colonization the number of IgA+ cells and CD11b+ IgA+ cells increased in the lamina propria of the colon and mediated an elevated IgA response upon E. faecium colonization.
Insights
Antibiotics disrupt gut mucus, allowing multidrug-resistant Enterococcus faecium to colonize rapidly within 6 hours. This early colonization triggers an immune response involving IgA+ cells in the colon.
Area of Science:
- Microbiology
- Immunology
- Gastroenterology
Background:
- Antibiotics disrupt the gut microbiota, promoting the growth of antibiotic-resistant bacteria like multidrug-resistant Enterococcus faecium.
- The initial stages of E. faecium colonization and outgrowth in antibiotic-treated hosts are not well understood.
Purpose of the Study:
- To investigate the early events of intestinal colonization by multidrug-resistant E. faecium in antibiotic-treated mice.
- To visualize the interaction between E. faecium and the intestinal epithelium.
Main Methods:
- Cephalosporin treatment of mice followed by E. faecium inoculation.
- Microscopic analysis of the intestinal mucus layer and epithelial junctions (E-cadherin, cadherin-17).
- Quantification of immune cells (IgA+ and CD11b+ IgA+ cells) in the colon lamina propria.
Main Results:
- Cephalosporin treatment rapidly reduced the Muc-2 mucus layer and altered E-cadherin junctions within 6 hours.
- E. faecium colonized the mouse colon within 6 hours, adhering to the intestinal epithelium.
- An increase in IgA+ and CD11b+ IgA+ cells was observed in the colon lamina propria, indicating an elevated IgA response.
Conclusions:
- Early antibiotic exposure creates a permissive environment for rapid E. faecium colonization.
- The intestinal epithelium's integrity is compromised early in antibiotic treatment, facilitating bacterial adhesion.
- An innate immune response, involving IgA, is mounted against E. faecium during early colonization.
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