ArticleNature microbiology2022
Enterotoxin tilimycin from gut-resident Klebsiella promotes mutational evolution and antibiotic resistance in mice.
Article in Nature microbiology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 32 citations in OpenAlex.
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- Feasibility and Safety of Washed Microbiota Transplantation as Salvage Therapy for Refractory Non-CDI Gut Pathogens in Critically Ill Patients.Microbial biotechnology · 2026Article
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- New Postbiotic Derived from Sequential Fermentation of TwoMicroorganisms · 2026Article
- Microbiome-mediated colonization resistance to and countermeasures of Klebsiella pneumoniae.Nature communications · 2026Article
- Clinical, microbial and metabolic characteristics of gas-forming pyogenic liver abscess and its potential formation mechanism.Frontiers in cellular and infection microbiology · 2026Article
- Refining microbiome resolution: KoSCAPEGut microbes · 2025Article
- Protein Engineering of Biosynthetic Enzymes Unlocks Libraries of Bioactive Tilimycin Analogs.ACS catalysis · 2025Article
- Suppression of gut colonization by multidrug-resistant Escherichia coli clinical isolates through cooperative niche exclusion.Nature communications · 2025Article
- Elevated antibiotic resistance gene abundance of ICU healthcare workers, a multicentre, cross-sectional study.Critical care (London, England) · 2025Observational
- Comprehensive analysis of gut microbiota and fecal metabolites in patients with autism spectrum disorder.Frontiers in microbiology · 2025Article
- Klebsiella oxytoca inhibits Salmonella infection through multiple microbiota-context-dependent mechanisms.Nature microbiology · 2024Article
- Non-Canonical Aspects of Antibiotics and Antibiotic Resistance.Antibiotics (Basel, Switzerland) · 2024Review
- An adapted method for Cas9-mediated editing reveals the species-specific role of β-glucoside utilization driving competition betweenJournal of bacteriology · 2024Article
- Animal models ofFrontiers in microbiology · 2024Review
- Reactive oxygen species accelerateiScience · 2023Article
- High-resolution microbiome analysis reveals exclusionary Klebsiella species competition in preterm infants at risk for necrotizing enterocolitis.Scientific reports · 2023Article
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.