Selected Publication:

SHR Neuro Cancer Cardio Lipid Metab Microb

Pöltl, L; Kitsera, M; Raffl, S; Schild, S; Cosic, A; Kienesberger, S; Unterhauser, K; Raber, G; Lembacher-Fadum, C; Breinbauer, R; Gorkiewicz, G; Sebastian, C; Hoefler, G; Zechner, EL.
Microbiota-derived genotoxin tilimycin generates colonic stem cell mutations.
Cell Rep. 2023; 42(3):112199 Doi: 10.1016/j.celrep.2023.112199
Web of Science PubMed FullText FullText_MUG

 

Co-authors Med Uni Graz

Gorkiewicz Gregor

Höfler Gerald

Kienesberger-Feist Sabine

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Abstract:

The DNA-alkylating metabolite tilimycin is a microbial genotoxin. Intestinal accumulation of tilimycin in individuals carrying til+ Klebsiella spp. causes apoptotic erosion of the epithelium and colitis. Renewal of the intestinal lining and response to injury requires the activities of stem cells located at the base of intestinal crypts. This study interrogates the consequences of tilimycin-induced DNA damage to cycling stem cells. We charted the spatial distribution and luminal quantities of til metabolites in Klebsiella-colonized mice in the context of a complex microbial community. Loss of marker gene G6pd function indicates genetic aberrations in colorectal stem cells that became stabilized in monoclonal mutant crypts. Mice colonized with tilimycin-producing Klebsiella displayed both higher frequencies of somatic mutation and more mutations per affected individual than animals carrying a non-producing mutant. Our findings imply that genotoxic til+ Klebsiella may drive somatic genetic change in the colon and increase disease susceptibility in human hosts.

Find related publications in this database (using NLM MeSH Indexing)

Humans - administration & dosage

Mice - administration & dosage

Animals - administration & dosage

Mutagens - metabolism

Colon - metabolism

Mutation - genetics

Microbiota - administration & dosage

Stem Cells - administration & dosage

Intestinal Mucosa - administration & dosage

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