Related Experiment Video
Updated: Jun 24, 2025
Chronic Salmonella Infection Induced Intestinal Fibrosis
Published on: September 22, 2019
Klebsiella oxytoca inhibits Salmonella infection through multiple microbiota-context-dependent mechanisms
Lisa Osbelt1,2,3, Éva D H Almási1, Marie Wende1,2
1Department of Microbial Immune Regulation, Helmholtz Center for Infection Research, Braunschweig, Germany.
Abstract:
The Klebsiella oxytoca species complex is part of the human microbiome, especially during infancy and childhood. K. oxytoca species complex strains can produce enterotoxins, namely, tilimycin and tilivalline, while also contributing to colonization resistance (CR). The relationship between these seemingly contradictory roles is not well understood. Here, by coupling ex vivo assays with CRISPR-mutagenesis and various mouse models, we show that K. oxytoca provides CR against Salmonella Typhimurium. In vitro, the antimicrobial activity against various Salmonella strains depended on tilimycin production and was induced by various simple carbohydrates. In vivo, CR against Salmonella depended on toxin production in germ-free mice, while it was largely toxin-independent in mice with residual microbiota. This was linked to the relative levels of toxin-inducing carbohydrates in vivo. Finally, dulcitol utilization was essential for toxin-independent CR in gnotobiotic mice. Together, this demonstrates that nutrient availability is key to both toxin-dependent and substrate-driven competition between K. oxytoca and Salmonella.
Insights
Klebsiella oxytoca provides colonization resistance against Salmonella Typhimurium. Nutrient availability influences this interaction, affecting toxin production and competition.
Area of Science:
- Microbiology
- Human Microbiome Research
- Infectious Disease Dynamics
Background:
- Klebsiella oxytoca species complex is a human gut microbe, particularly in children.
- K. oxytoca produces enterotoxins (tilimycin, tilivalline) and aids colonization resistance (CR).
- The dual role of K. oxytoca in producing toxins and promoting CR is poorly understood.
Purpose of the Study:
- To elucidate the relationship between K. oxytoca's toxin production and its role in colonization resistance against Salmonella Typhimurium.
- To investigate the influence of nutrient availability on this host-microbe interaction.
Main Methods:
- Ex vivo assays and CRISPR-mutagenesis were employed.
- Various mouse models, including germ-free and gnotobiotic mice, were utilized.
- In vitro and in vivo experiments assessed antimicrobial activity and colonization resistance.
Main Results:
- K. oxytoca demonstrated in vitro antimicrobial activity against Salmonella, dependent on tilimycin production and simple carbohydrates.
- In vivo, CR against Salmonella was toxin-dependent in germ-free mice but largely toxin-independent in mice with residual microbiota.
- Nutrient availability, specifically toxin-inducing carbohydrates and dulcitol utilization, modulated CR.
Conclusions:
- Nutrient availability is a critical factor governing both toxin-dependent and substrate-driven competition between K. oxytoca and Salmonella.
- K. oxytoca's contribution to colonization resistance is context-dependent, influenced by the microbiome and available nutrients.
- Understanding these dynamics is crucial for microbiome-based therapeutic strategies.
