title: Gene fitness landscapes of Vibrio cholerae at important stages of its life cycle.
abstract: Vibrio cholerae has evolved to adeptly transition between the human small intestine and aquatic environments, leading to water-borne spread and transmission of the lethal diarrheal disease cholera. Using a host model that mimics the pathology of human cholera, we applied high density transposon mutagenesis combined with massively parallel sequencing (Tn-seq) to determine the fitness contribution of >90% of all non-essential genes of V. cholerae both during host infection and dissemination. Targeted mutagenesis and validation of 35 genes confirmed our results for the selective conditions with a total false positive rate of 4%. We identified 165 genes never before implicated for roles in dissemination that reside within pathways controlling many metabolic, catabolic and protective processes, from which a central role for glycogen metabolism was revealed. We additionally identified 76 new pathogenicity factors and 414 putatively essential genes for V. cholerae growth. Our results provide a comprehensive framework for understanding the biology of V. cholerae as it colonizes the small intestine, elicits profuse secretory diarrhea, and disseminates into the aquatic environment.
authors.affiliation: Howard Hughes Medical Institute and Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts, United States of America.
authors.forename: Heather D
authors.initials: HD
authors.lastname: Kamp
authors.affiliation: Howard Hughes Medical Institute and Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts, United States of America.
authors.forename: Bharathi
authors.initials: B
authors.lastname: Patimalla-Dipali
authors.affiliation: Howard Hughes Medical Institute and Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts, United States of America.
authors.forename: David W
authors.initials: DW
authors.lastname: Lazinski
authors.affiliation: Howard Hughes Medical Institute and Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts, United States of America.
authors.forename: Faith
authors.initials: F
authors.lastname: Wallace-Gadsden
authors.affiliation: Howard Hughes Medical Institute and Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts, United States of America.
authors.forename: Andrew
authors.initials: A
authors.lastname: Camilli
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics; D000818:Animals; D000831:Animals, Newborn; D056084:Genetic Fitness; D016680:Genome, Bacterial; D059014:High-Throughput Nucleotide Sequencing; D054884:Host-Pathogen Interactions; D008018:Life Cycle Stages / Q000235:genetics*; D050296:Microbial Viability / Q000235:genetics; D030781:Organisms, Genetically Modified; D011817:Rabbits; D014734:Vibrio cholerae / Q000235:genetics* / Q000254:growth & development*; D014867:Water
chemical_list: D014867:Water