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  1. Artikel ; Online: Defence and adaptation mechanisms of the intestinal epithelium upon infection.

    Iftekhar, Amina / Sigal, Michael

    International journal of medical microbiology : IJMM

    2021  Band 311, Heft 3, Seite(n) 151486

    Abstract: The intestinal epithelium is a monolayer of polarized columnar cells that act as a border between the host and its environment and are the first line of defence against the luminal microbes. In addition to providing a physical barrier, the epithelium ... ...

    Abstract The intestinal epithelium is a monolayer of polarized columnar cells that act as a border between the host and its environment and are the first line of defence against the luminal microbes. In addition to providing a physical barrier, the epithelium possesses a multitude of active mechanisms to fight invading pathogens and regulate the composition and spatial distribution of commensals. The different epithelial cell types have unique functions in this context, and crosstalk with the immune system further modulates their intricate antimicrobial responses. The epithelium is organized into clonal crypt units with a high cellular turnover that is driven by stem cells located at the base. There is increasing evidence that this anatomical organization, the stem cell turnover, and the lineage determination processes are essential for barrier maintenance. These processes can be modulated by microbes directly or by the immune responses to enteric pathogens, resulting in a rapid and efficient adaptation of the epithelium to environmental perturbations, injuries, and infections. Here we discuss the complex host-microbial interactions that shape the mucosa and how the epithelium maintains and re-establishes homeostasis after infection.
    Mesh-Begriff(e) Cells, Cultured ; Epithelial Cells ; Epithelium ; Homeostasis ; Intestinal Mucosa
    Sprache Englisch
    Erscheinungsdatum 2021-02-25
    Erscheinungsland Germany
    Dokumenttyp Journal Article
    ZDB-ID 2006518-8
    ISSN 1618-0607 ; 1438-4221
    ISSN (online) 1618-0607
    ISSN 1438-4221
    DOI 10.1016/j.ijmm.2021.151486
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel ; Online: Genomic aberrations after short-term exposure to colibactin-producing E. coli transform primary colon epithelial cells.

    Iftekhar, Amina / Berger, Hilmar / Bouznad, Nassim / Heuberger, Julian / Boccellato, Francesco / Dobrindt, Ulrich / Hermeking, Heiko / Sigal, Michael / Meyer, Thomas F

    Nature communications

    2021  Band 12, Heft 1, Seite(n) 1003

    Abstract: Genotoxic colibactin-producing pks+ Escherichia coli induce DNA double-strand breaks, mutations, and promote tumor development in mouse models of colorectal cancer (CRC). Colibactin's distinct mutational signature is reflected in human CRC, suggesting a ... ...

    Abstract Genotoxic colibactin-producing pks+ Escherichia coli induce DNA double-strand breaks, mutations, and promote tumor development in mouse models of colorectal cancer (CRC). Colibactin's distinct mutational signature is reflected in human CRC, suggesting a causal link. Here, we investigate its transformation potential using organoids from primary murine colon epithelial cells. Organoids recovered from short-term infection with pks+ E. coli show characteristics of CRC cells, e.g., enhanced proliferation, Wnt-independence, and impaired differentiation. Sequence analysis of Wnt-independent organoids reveals an enhanced mutational burden, including chromosomal aberrations typical of genomic instability. Although we do not find classic Wnt-signaling mutations, we identify several mutations in genes related to p53-signaling, including miR-34a. Knockout of Trp53 or miR-34 in organoids results in Wnt-independence, corroborating a functional interplay between the p53 and Wnt pathways. We propose larger chromosomal alterations and aneuploidy as the basis of transformation in these organoids, consistent with the early appearance of chromosomal instability in CRC.
    Mesh-Begriff(e) Animals ; Chromosome Aberrations ; Colon/pathology ; Colonic Neoplasms/genetics ; Colonic Neoplasms/pathology ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/psychology ; DNA Damage ; Epithelial Cells/metabolism ; Epithelial Cells/pathology ; Escherichia coli/genetics ; Escherichia coli/metabolism ; Genomics ; Male ; Mice ; Mice, Knockout ; Mutation ; Organoids ; Peptides/genetics ; Peptides/metabolism ; Polyketides/metabolism
    Chemische Substanzen Peptides ; Polyketides ; colibactin
    Sprache Englisch
    Erscheinungsdatum 2021-02-12
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-021-21162-y
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel ; Online: Genotoxic Effect of

    Sepe, Ludovico P / Hartl, Kimberly / Iftekhar, Amina / Berger, Hilmar / Kumar, Naveen / Goosmann, Christian / Chopra, Sascha / Schmidt, Sven Christian / Gurumurthy, Rajendra Kumar / Meyer, Thomas F / Boccellato, Francesco

    mBio

    2020  Band 11, Heft 5

    Abstract: Carcinoma of the gallbladder (GBC) is the most frequent tumor of the biliary tract. Despite epidemiological studies showing a correlation between chronic infection ... ...

    Abstract Carcinoma of the gallbladder (GBC) is the most frequent tumor of the biliary tract. Despite epidemiological studies showing a correlation between chronic infection with
    Mesh-Begriff(e) Adult ; Aged ; Animals ; Cells, Cultured ; DNA Damage ; Epithelial Cells/microbiology ; Epithelial Cells/pathology ; Female ; Gallbladder/cytology ; Gallbladder/microbiology ; Host-Pathogen Interactions ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Middle Aged ; Salmonella paratyphi A/pathogenicity ; Serogroup ; Virulence/genetics
    Sprache Englisch
    Erscheinungsdatum 2020-09-22
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ZDB-ID 2557172-2
    ISSN 2150-7511 ; 2161-2129
    ISSN (online) 2150-7511
    ISSN 2161-2129
    DOI 10.1128/mBio.01911-20
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  4. Artikel ; Online: Colibactin DNA-damage signature indicates mutational impact in colorectal cancer.

    Dziubańska-Kusibab, Paulina J / Berger, Hilmar / Battistini, Federica / Bouwman, Britta A M / Iftekhar, Amina / Katainen, Riku / Cajuso, Tatiana / Crosetto, Nicola / Orozco, Modesto / Aaltonen, Lauri A / Meyer, Thomas F

    Nature medicine

    2020  Band 26, Heft 7, Seite(n) 1063–1069

    Abstract: The mucosal epithelium is a common target of damage by chronic bacterial infections and the accompanying toxins, and most cancers originate from this tissue. We investigated whether colibactin, a potent ... ...

    Abstract The mucosal epithelium is a common target of damage by chronic bacterial infections and the accompanying toxins, and most cancers originate from this tissue. We investigated whether colibactin, a potent genotoxin
    Mesh-Begriff(e) Cell Line, Tumor ; Cell Proliferation/drug effects ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/microbiology ; Colorectal Neoplasms/pathology ; DNA Breaks, Double-Stranded/drug effects ; DNA Damage/drug effects ; Epithelial Cells/drug effects ; Escherichia coli/pathogenicity ; Humans ; Mutation/drug effects ; Nucleotide Motifs/drug effects ; Peptides/pharmacology ; Polyketides/pharmacology
    Chemische Substanzen Peptides ; Polyketides ; colibactin
    Sprache Englisch
    Erscheinungsdatum 2020-06-01
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1220066-9
    ISSN 1546-170X ; 1078-8956
    ISSN (online) 1546-170X
    ISSN 1078-8956
    DOI 10.1038/s41591-020-0908-2
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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