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Salmonella Typhimurium Diarrhea Reveals Basic Principles of Enteropathogen Infection and Disease-Promoted DNA
Sandra Y Wotzka1, Bidong D Nguyen1, Wolf-Dietrich Hardt1
1Institute of Microbiology, ETH Zurich, 8093 Zurich, Switzerland.
Abstract:
Despite decades of research, efficient therapies for most enteropathogenic bacteria are still lacking. In this review, we focus on Salmonella enterica Typhimurium (S. Typhimurium), a frequent cause of acute, self-limiting food-borne diarrhea and a model that has revealed key principles of enteropathogen infection. We review the steps of gut infection and the mucosal innate-immune defenses limiting pathogen burdens, and we discuss how inflammation boosts gut luminal S. Typhimurium growth. We also discuss how S. Typhimurium-induced inflammation accelerates the transfer of plasmids and phages, which may promote the transmission of antibiotic resistance and facilitate emergence of pathobionts and pathogens with enhanced virulence. The targeted manipulation of the microbiota and vaccination might offer strategies to prevent this evolution. As gut luminal microbes impact various aspects of the host's physiology, improved strategies for preventing enteropathogen infection and disease-inflicted DNA exchange may be of broad interest well beyond the acute infection.
Insights
Salmonella Typhimurium infection triggers inflammation, which can accelerate antibiotic resistance gene transfer and pathogen evolution. Strategies like microbiota manipulation and vaccination may prevent these detrimental outcomes.
Area of Science:
- Microbiology
- Immunology
- Gastroenterology
Background:
- Efficient therapies for enteropathogenic bacteria remain a challenge.
- Salmonella enterica Typhimurium (S. Typhimurium) is a model enteropathogen causing food-borne diarrhea.
- Understanding S. Typhimurium infection mechanisms is crucial for developing effective treatments.
Purpose of the Study:
- To review the infection process of S. Typhimurium in the gut.
- To discuss innate-immune responses and inflammation's role in S. Typhimurium infection.
- To explore how inflammation promotes horizontal gene transfer and pathogen evolution.
Main Methods:
- Literature review of S. Typhimurium pathogenesis.
- Analysis of host-pathogen interactions and immune defenses.
- Discussion of microbial genetics and evolution in the gut environment.
Main Results:
- Inflammation significantly enhances S. Typhimurium growth in the gut lumen.
- S. Typhimurium-induced inflammation accelerates plasmid and phage transfer.
- This process can promote antibiotic resistance and virulence evolution.
Conclusions:
- Targeted microbiota manipulation and vaccination are potential preventative strategies.
- Controlling enteropathogen infection and DNA exchange is vital for public health.
- Insights into gut microbial dynamics have broad implications beyond acute infections.