Klebsiella pneumoniae employs a type VI secretion system to overcome microbiota-mediated colonization resistance
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 th...
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| Format: | Article |
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56309-8 |
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| author | Andrew S. Bray Christopher A. Broberg Andrew W. Hudson Weisheng Wu Ravinder K. Nagpal Maidul Islam Juan D. Valencia-Bacca Fawaz Shahid Giovanna E. Hernandez Noah A. Nutter Kimberly A. Walker Emma F. Bennett Taylor M. Young Andrew J. Barnes David A. Ornelles Virginia L. Miller M. Ammar Zafar |
| author_facet | Andrew S. Bray Christopher A. Broberg Andrew W. Hudson Weisheng Wu Ravinder K. Nagpal Maidul Islam Juan D. Valencia-Bacca Fawaz Shahid Giovanna E. Hernandez Noah A. Nutter Kimberly A. Walker Emma F. Bennett Taylor M. Young Andrew J. Barnes David A. Ornelles Virginia L. Miller M. Ammar Zafar |
| author_sort | Andrew S. Bray |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-0253ef103c0a426590bba9fa2c766492 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-0253ef103c0a426590bba9fa2c7664922025-01-26T12:42:01ZengNature PortfolioNature Communications2041-17232025-01-0116111710.1038/s41467-025-56309-8Klebsiella pneumoniae employs a type VI secretion system to overcome microbiota-mediated colonization resistanceAndrew S. Bray0Christopher A. Broberg1Andrew W. Hudson2Weisheng Wu3Ravinder K. Nagpal4Maidul Islam5Juan D. Valencia-Bacca6Fawaz Shahid7Giovanna E. Hernandez8Noah A. Nutter9Kimberly A. Walker10Emma F. Bennett11Taylor M. Young12Andrew J. Barnes13David A. Ornelles14Virginia L. Miller15M. Ammar Zafar16Department of Microbiology and Immunology, Wake Forest School of MedicineDepartment of Microbiology and Immunology, University of North Carolina School of MedicineDepartment of Microbiology and Immunology, Wake Forest School of MedicineBRCF Bioinformatics Core, University of MichiganDepartment of Nutrition & Integrative Physiology, Florida State University College of Health and Human SciencesDepartment of Microbiology and Immunology, Wake Forest School of MedicineDepartment of Microbiology and Immunology, Wake Forest School of MedicineWake Forest University, Winston SalemDepartment of Microbiology and Immunology, Wake Forest School of MedicineDepartment of Microbiology and Immunology, Wake Forest School of MedicineDepartment of Microbiology and Immunology, University of North Carolina School of MedicineDepartment of Microbiology and Immunology, Wake Forest School of MedicineDepartment of Microbiology and Immunology, Wake Forest School of MedicineDepartment of Microbiology and Immunology, Wake Forest School of MedicineDepartment of Microbiology and Immunology, Wake Forest School of MedicineDepartment of Microbiology and Immunology, University of North Carolina School of MedicineDepartment of Microbiology and Immunology, Wake Forest School of MedicineAbstract 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.https://doi.org/10.1038/s41467-025-56309-8 |
| spellingShingle | Andrew S. Bray Christopher A. Broberg Andrew W. Hudson Weisheng Wu Ravinder K. Nagpal Maidul Islam Juan D. Valencia-Bacca Fawaz Shahid Giovanna E. Hernandez Noah A. Nutter Kimberly A. Walker Emma F. Bennett Taylor M. Young Andrew J. Barnes David A. Ornelles Virginia L. Miller M. Ammar Zafar Klebsiella pneumoniae employs a type VI secretion system to overcome microbiota-mediated colonization resistance Nature Communications |
| title | Klebsiella pneumoniae employs a type VI secretion system to overcome microbiota-mediated colonization resistance |
| title_full | Klebsiella pneumoniae employs a type VI secretion system to overcome microbiota-mediated colonization resistance |
| title_fullStr | Klebsiella pneumoniae employs a type VI secretion system to overcome microbiota-mediated colonization resistance |
| title_full_unstemmed | Klebsiella pneumoniae employs a type VI secretion system to overcome microbiota-mediated colonization resistance |
| title_short | Klebsiella pneumoniae employs a type VI secretion system to overcome microbiota-mediated colonization resistance |
| title_sort | klebsiella pneumoniae employs a type vi secretion system to overcome microbiota mediated colonization resistance |
| url | https://doi.org/10.1038/s41467-025-56309-8 |
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