Enterotoxin tilimycin from gut-resident Klebsiella promotes mutational evolution and antibiotic resistance in mice.
Journal
Nature microbiology
ISSN: 2058-5276
Titre abrégé: Nat Microbiol
Pays: England
ID NLM: 101674869
Informations de publication
Date de publication:
11 2022
11 2022
Historique:
received:
27
03
2022
accepted:
29
09
2022
pubmed:
28
10
2022
medline:
1
11
2022
entrez:
27
10
2022
Statut:
ppublish
Résumé
Klebsiella spp. that secrete the DNA-alkylating enterotoxin tilimycin colonize the human intestinal tract. Numbers of toxigenic bacteria increase during antibiotic use, and the resulting accumulation of tilimycin in the intestinal lumen damages the epithelium via genetic instability and apoptosis. Here we examine the impact of this genotoxin on the gut ecosystem. 16S rRNA sequencing of faecal samples from mice colonized with Klebsiella oxytoca strains and mechanistic analyses show that tilimycin is a pro-mutagenic antibiotic affecting multiple phyla. Transient synthesis of tilimycin in the murine gut antagonized niche competitors, reduced microbial richness and altered taxonomic composition of the microbiota both during and following exposure. Moreover, tilimycin secretion increased rates of mutagenesis in co-resident opportunistic pathogens such as Klebsiella pneumoniae and Escherichia coli, as shown by de novo acquisition of antibiotic resistance. We conclude that tilimycin is a bacterial mutagen, and flares of genotoxic Klebsiella have the potential to drive the emergence of resistance, destabilize the gut microbiota and shape its evolutionary trajectory.
Identifiants
pubmed: 36289400
doi: 10.1038/s41564-022-01260-3
pii: 10.1038/s41564-022-01260-3
pmc: PMC9613472
doi:
Substances chimiques
Anti-Bacterial Agents
0
Enterotoxins
0
RNA, Ribosomal, 16S
0
tilimycin
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1834-1848Subventions
Organisme : Austrian Science Fund FWF
ID : DOC 50
Pays : Austria
Informations de copyright
© 2022. The Author(s).
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