Back to Search
Start Over
Gene fitness landscapes of Vibrio cholerae at important stages of its life cycle
- Source :
- PLoS Pathogens, Vol 9, Iss 12, p e1003800 (2013), PLoS Pathogens
- Publication Year :
- 2013
- Publisher :
- Public Library of Science (PLoS), 2013.
-
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.<br />Author Summary Cholera is a deadly diarrheal disease that spreads in explosive epidemics and is caused by the water-borne bacterium Vibrio cholerae. Pathogenic strains of V. cholerae can be found in both fresh and salt water estuaries in-between cholera outbreaks. Cholera infections are frequently derived from contaminated fresh water sources. In this study, we sought to determine on a genome-wide scale how V. cholerae is able to colonize and proliferate in the nutrient-rich environment of the small intestine, but then also survive dissemination and persist in the nutrient-limited aquatic environment. Using a host model that mimics the pathology of human cholera, we utilized genome-wide transposon mutagenesis and massively parallel sequencing of the insertion junctions to obtain the relative fitness of V. cholerae mutants during infection and dissemination. This extensive data set represents the first genetic screen of any kind to identify genes important for dissemination into the environment and has broad significance for understanding and controlling the spread and persistence of Vibrio cholerae and potentially other water-borne pathogens in the environment.
- Subjects :
- lcsh:Immunologic diseases. Allergy
Immunology
Genetic Fitness
Mutagenesis (molecular biology technique)
Biology
medicine.disease_cause
Microbiology
Genome
03 medical and health sciences
Virology
Genetics
medicine
Animals
Vibrio cholerae
Molecular Biology
Gene
lcsh:QH301-705.5
030304 developmental biology
Life Cycle Stages
0303 health sciences
Microbial Viability
Massive parallel sequencing
Organisms, Genetically Modified
030306 microbiology
High-Throughput Nucleotide Sequencing
Water
medicine.disease
Adaptation, Physiological
Cholera
3. Good health
Animals, Newborn
lcsh:Biology (General)
Host-Pathogen Interactions
Parasitology
Transposon mutagenesis
Rabbits
lcsh:RC581-607
Genome, Bacterial
Research Article
Subjects
Details
- Language :
- English
- ISSN :
- 15537374 and 15537366
- Volume :
- 9
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- PLoS Pathogens
- Accession number :
- edsair.doi.dedup.....934ed3a7ce6f15131af3dae9fd75b1fb