Cyclic-di-AMP confers an invasive phenotype on Escherichia coli through elongation of flagellin filaments
Abstract Background Adherent-invasive Escherichia coli (AIEC) is isolated from patients with Crohn’s disease (CD). AIEC can invade the intestinal epithelium, suggesting that it is involved in the development and pathogenesis of CD. However, the mechanism by which AIEC acquired the invasive phenotype...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2024-01-01
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| Series: | Gut Pathogens |
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| Online Access: | https://doi.org/10.1186/s13099-024-00600-4 |
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| author | Rika Tanaka Jin Imai Eiji Sugiyama Shogo Tsubaki Katsuto Hozumi Hitoshi Tsugawa |
| author_facet | Rika Tanaka Jin Imai Eiji Sugiyama Shogo Tsubaki Katsuto Hozumi Hitoshi Tsugawa |
| author_sort | Rika Tanaka |
| collection | DOAJ |
| description | Abstract Background Adherent-invasive Escherichia coli (AIEC) is isolated from patients with Crohn’s disease (CD). AIEC can invade the intestinal epithelium, suggesting that it is involved in the development and pathogenesis of CD. However, the mechanism by which AIEC acquired the invasive phenotype remains unknown. Results This study was designed to examine the mechanisms of AIEC invasiveness. We found that the flagellin (fliC) expression in AIEC was two-fold higher than that in non-AIEC strains, and this overexpression induced the formation of long-filament flagellin. Deletion of fliC in the AIEC LF82 strain resulted in the disappearance of flagellar filaments and attenuated the motility and invasive ability of the bacterium, suggesting that the formation of long filament flagellin induced by increased fliC expression is required by AIEC to invade the intestinal epithelium. In AIEC and non-AIEC K12 strains cultured in the presence of cyclic-di-AMP (c-di-AMP), the expression of fliC was enhanced, and flagellar filaments were elongated. Stimulation with c-di-AMP enhanced the bacterial motility and ability to invade epithelial cells, even in the non-AIEC K12 strain. Conclusions Our findings show that c-di-AMP confers an AIEC-like phenotype on non-AIEC strains by enhancing the expression of fliC. The results should be useful for understanding the pathogenesis of CD. |
| first_indexed | 2024-03-07T15:30:10Z |
| format | Article |
| id | doaj.art-e351970832114a5b81ed1865e212995f |
| institution | Directory Open Access Journal |
| issn | 1757-4749 |
| language | English |
| last_indexed | 2024-03-07T15:30:10Z |
| publishDate | 2024-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Gut Pathogens |
| spelling | doaj.art-e351970832114a5b81ed1865e212995f2024-03-05T16:31:07ZengBMCGut Pathogens1757-47492024-01-0116111110.1186/s13099-024-00600-4Cyclic-di-AMP confers an invasive phenotype on Escherichia coli through elongation of flagellin filamentsRika Tanaka0Jin Imai1Eiji Sugiyama2Shogo Tsubaki3Katsuto Hozumi4Hitoshi Tsugawa5Department of Immunology, Division of Host Defense Mechanism, Tokai University School of MedicineDepartment of Clinical Health Science, Tokai University School of MedicineLaboratory of Analytical and Bio-Analytical Chemistry, School of Pharmaceutical Sciences, University of ShizuokaTranskingdom Signaling Research Unit, Division of Host Defense Mechanism, Tokai University School of MedicineDepartment of Immunology, Division of Host Defense Mechanism, Tokai University School of MedicineTranskingdom Signaling Research Unit, Division of Host Defense Mechanism, Tokai University School of MedicineAbstract Background Adherent-invasive Escherichia coli (AIEC) is isolated from patients with Crohn’s disease (CD). AIEC can invade the intestinal epithelium, suggesting that it is involved in the development and pathogenesis of CD. However, the mechanism by which AIEC acquired the invasive phenotype remains unknown. Results This study was designed to examine the mechanisms of AIEC invasiveness. We found that the flagellin (fliC) expression in AIEC was two-fold higher than that in non-AIEC strains, and this overexpression induced the formation of long-filament flagellin. Deletion of fliC in the AIEC LF82 strain resulted in the disappearance of flagellar filaments and attenuated the motility and invasive ability of the bacterium, suggesting that the formation of long filament flagellin induced by increased fliC expression is required by AIEC to invade the intestinal epithelium. In AIEC and non-AIEC K12 strains cultured in the presence of cyclic-di-AMP (c-di-AMP), the expression of fliC was enhanced, and flagellar filaments were elongated. Stimulation with c-di-AMP enhanced the bacterial motility and ability to invade epithelial cells, even in the non-AIEC K12 strain. Conclusions Our findings show that c-di-AMP confers an AIEC-like phenotype on non-AIEC strains by enhancing the expression of fliC. The results should be useful for understanding the pathogenesis of CD.https://doi.org/10.1186/s13099-024-00600-4Adherent-invasive Escherichia coli (AIEC)Cyclic di-adenosine monophosphate (c-di-AMP)Crohn’s diseaseFlagellin filamentInflammatory bowel disease (IBD)Intestinal epithelium |
| spellingShingle | Rika Tanaka Jin Imai Eiji Sugiyama Shogo Tsubaki Katsuto Hozumi Hitoshi Tsugawa Cyclic-di-AMP confers an invasive phenotype on Escherichia coli through elongation of flagellin filaments Gut Pathogens Adherent-invasive Escherichia coli (AIEC) Cyclic di-adenosine monophosphate (c-di-AMP) Crohn’s disease Flagellin filament Inflammatory bowel disease (IBD) Intestinal epithelium |
| title | Cyclic-di-AMP confers an invasive phenotype on Escherichia coli through elongation of flagellin filaments |
| title_full | Cyclic-di-AMP confers an invasive phenotype on Escherichia coli through elongation of flagellin filaments |
| title_fullStr | Cyclic-di-AMP confers an invasive phenotype on Escherichia coli through elongation of flagellin filaments |
| title_full_unstemmed | Cyclic-di-AMP confers an invasive phenotype on Escherichia coli through elongation of flagellin filaments |
| title_short | Cyclic-di-AMP confers an invasive phenotype on Escherichia coli through elongation of flagellin filaments |
| title_sort | cyclic di amp confers an invasive phenotype on escherichia coli through elongation of flagellin filaments |
| topic | Adherent-invasive Escherichia coli (AIEC) Cyclic di-adenosine monophosphate (c-di-AMP) Crohn’s disease Flagellin filament Inflammatory bowel disease (IBD) Intestinal epithelium |
| url | https://doi.org/10.1186/s13099-024-00600-4 |
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