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Klebsiella pneumoniae employs a type VI secretion system to overcome microbiota-mediated colonization resistance
Andrew S Bray1, Christopher A Broberg2, Andrew W Hudson1
1Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston Salem, NC, USA.
Abstract:
Microbial species must compete for space and nutrients to persist in the gastrointestinal (GI) tract, and our understanding of the complex pathobiont-microbiota interactions is far from complete. Klebsiella pneumoniae, a problematic, often drug-resistant nosocomial pathogen, can colonize the GI tract asymptomatically, serving as an infection reservoir. To provide insight on how K. pneumoniae interacts with the resident gut microbiome, we conduct a transposon mutagenesis screen using a murine model of GI colonization with an intact microbiota. Among the genes identified were those encoding a type VI secretion system (T6SS), which mediates contact-dependent killing of gram-negative bacteria. From several approaches, we demonstrate that the T6SS is critical for K. pneumoniae gut colonization. Metagenomics and in vitro killing assays reveal that K. pneumoniae reduces Betaproteobacteria species in a T6SS-dependent manner, thus identifying specific species targeted by K. pneumoniae. We further show that T6SS gene expression is controlled by several transcriptional regulators and that expression only occurs in vitro under conditions that mimic the gut environment. By enabling K. pneumoniae to thrive in the gut, the T6SS indirectly contributes to the pathogenic potential of this organism. These observations advance our molecular understanding of how K. pneumoniae successfully colonizes the GI tract.
Insights
Klebsiella pneumoniae uses a type VI secretion system (T6SS) to colonize the gut by killing competing bacteria, particularly Betaproteobacteria. This mechanism enhances its ability to thrive and potentially cause infection.
Area of Science:
- Microbiology
- Gastroenterology
- Pathogen-Host Interactions
Background:
- The gastrointestinal tract harbors complex microbial communities essential for health.
- Klebsiella pneumoniae is a significant nosocomial pathogen that can asymptomatically colonize the gut, acting as a reservoir for infections.
- Understanding how K. pneumoniae interacts with the resident gut microbiota is crucial for controlling its spread and pathogenicity.
Purpose of the Study:
- To investigate the molecular mechanisms by which Klebsiella pneumoniae colonizes the gastrointestinal tract.
- To identify specific microbial interactions and genetic factors involved in K. pneumoniae gut colonization.
- To elucidate the role of the type VI secretion system (T6SS) in K. pneumoniae's interaction with the gut microbiome.
Main Methods:
- A transposon mutagenesis screen was performed in a murine model of gastrointestinal colonization with an intact microbiota.
- Metagenomic analysis and in vitro killing assays were employed to assess bacterial interactions.
- Gene expression analysis was conducted to understand the regulation of T6SS in K. pneumoniae.
Main Results:
- The type VI secretion system (T6SS) was identified as critical for K. pneumoniae gut colonization.
- K. pneumoniae was shown to reduce Betaproteobacteria species in a T6SS-dependent manner, indicating targeted killing.
- T6SS gene expression is regulated by transcriptional factors and is induced under conditions mimicking the gut environment.
Conclusions:
- The T6SS is a key factor enabling Klebsiella pneumoniae to successfully colonize the gastrointestinal tract.
- This T6SS-mediated competition with the gut microbiota, specifically targeting Betaproteobacteria, indirectly enhances K. pneumoniae's pathogenic potential.
- These findings provide molecular insights into K. pneumoniae gut colonization and its implications for infectious disease.
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