title: Tn-Seq analysis of Vibrio cholerae intestinal colonization reveals a role for T6SS-mediated antibacterial activity in the host.
abstract: Analysis of genes required for host infection will provide clues to the drivers of evolutionary fitness of pathogens like Vibrio cholerae, a mounting threat to global heath. We used transposon insertion site sequencing (Tn-seq) to comprehensively assess the contribution of nearly all V. cholerae genes toward growth in the infant rabbit intestine. Four hundred genes were identified as critical to V. cholerae in vivo fitness. These included most known colonization factors and several new genes affecting the bacterium's metabolic properties, resistance to bile, and ability to synthesize cyclic AMP-GMP. Notably, a mutant carrying an insertion in tsiV3, encoding immunity to a bacteriocidal type VI secretion system (T6SS) effector VgrG3, exhibited a colonization defect. The reduced in vivo fitness of tsiV3 mutants depends on their cocolonization with bacterial cells carrying an intact T6SS locus and VgrG3 gene, suggesting that the V. cholerae T6SS is functional and mediates antagonistic interbacterial interactions during infection.
authors: Department of Microbiology and Immunobiology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA; College of Life Science, Nankai University, 94 Weijin Road, Tianjin 300071, China.
authors: Yang
authors: Y
authors: Fu
authors: Department of Microbiology and Immunobiology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA; Division of Infectious Disease, Brigham & Women's Hospital, and Howard Hughes Medical Institute, Boston, MA 02115, USA. Electronic address: mwaldor@research.bwh.harvard.edu.
authors: Matthew K
authors: MK
authors: Waldor
authors: Department of Microbiology and Immunobiology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA. Electronic address: john_mekalanos@hms.harvard.edu.
authors: John J
authors: JJ
authors: Mekalanos
mesh_terms: D000818:Animals; D000898:Antibiosis; D058947:Bacterial Secretion Systems; D004251:DNA Transposable Elements; D020869:Gene Expression Profiling; D054884:Host-Pathogen Interactions; D016254:Mutagenesis, Insertional; D011817:Rabbits; D017422:Sequence Analysis, DNA / Q000379:methods; D014734:Vibrio cholerae / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity / Q000502:physiology*
chemical_list: D058947:Bacterial Secretion Systems; D004251:DNA Transposable Elements