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Updated: Aug 8, 2025

Quantification of Colonic Stem Cell Mutations
07:53

Quantification of Colonic Stem Cell Mutations

Published on: September 25, 2015

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Microbiota-derived genotoxin tilimycin generates colonic stem cell mutations

Lisa Pöltl1, Maksym Kitsera1, Sandra Raffl1

  • 1Institute of Molecular Biosciences, University of Graz, 8010 Graz, Austria.

Cell Reports
|March 4, 2023
PubMed

Insights

Genotoxic bacteria like Klebsiella can cause DNA damage in intestinal stem cells, leading to mutations and increased disease risk. This study reveals how tilimycin, a bacterial toxin, impacts colon health.

Area of Science:

  • Microbiology
  • Genetics
  • Gastroenterology

Background:

  • The gut microbiome plays a crucial role in intestinal health.
  • Certain bacteria produce genotoxins that can harm host cells.
  • Intestinal stem cells are vital for tissue repair and regeneration.

Purpose of the Study:

  • To investigate the effects of the DNA-alkylating genotoxin tilimycin on intestinal stem cells.
  • To understand the link between tilimycin-producing Klebsiella and colorectal stem cell mutations.
  • To assess the impact of genotoxic bacteria on somatic genetic changes in the colon.

Main Methods:

  • Spatial distribution and quantification of tilimycin metabolites in colonized mice.
  • Analysis of genetic aberrations in colorectal stem cells using marker gene G6pd.
  • Comparison of mutation frequencies in mice colonized with tilimycin-producing versus non-producing Klebsiella.

Main Results:

  • Tilimycin accumulation was observed in Klebsiella-colonized mice.
  • Loss of G6pd function indicated genetic damage in colorectal stem cells, forming monoclonal mutant crypts.
  • Mice with tilimycin-producing Klebsiella showed significantly higher frequencies and burdens of somatic mutations.

Conclusions:

  • Genotoxic Klebsiella species can induce somatic genetic alterations in the colon.
  • Tilimycin-induced DNA damage to stem cells may contribute to disease susceptibility.
  • Understanding these microbial genotoxic effects is crucial for human gut health.
Keywords:
CP: Microbiologyantibioticsbacterial metabolitecolorectal epitheliumgenotoxingut microbiotaintestinal stem cellnecrotizing enterocolitissomatic mutation frequency

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