Gene fitness landscapes of Vibrio cholerae at important stages of its life cycle.

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 muta...

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Main Authors: Heather D Kamp, Bharathi Patimalla-Dipali, David W Lazinski, Faith Wallace-Gadsden, Andrew Camilli
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS Pathogens
Online Access:https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1003800&type=printable
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author Heather D Kamp
Bharathi Patimalla-Dipali
David W Lazinski
Faith Wallace-Gadsden
Andrew Camilli
author_facet Heather D Kamp
Bharathi Patimalla-Dipali
David W Lazinski
Faith Wallace-Gadsden
Andrew Camilli
author_sort Heather D Kamp
collection DOAJ
description 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.
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institution Kabale University
issn 1553-7366
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language English
publishDate 2013-01-01
publisher Public Library of Science (PLoS)
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spelling doaj-art-f3d4b7a97a44454ea7a026a2aa7c8f732025-01-16T05:30:59ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742013-01-01912e100380010.1371/journal.ppat.1003800Gene fitness landscapes of Vibrio cholerae at important stages of its life cycle.Heather D KampBharathi Patimalla-DipaliDavid W LazinskiFaith Wallace-GadsdenAndrew CamilliVibrio 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.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1003800&type=printable
spellingShingle Heather D Kamp
Bharathi Patimalla-Dipali
David W Lazinski
Faith Wallace-Gadsden
Andrew Camilli
Gene fitness landscapes of Vibrio cholerae at important stages of its life cycle.
PLoS Pathogens
title Gene fitness landscapes of Vibrio cholerae at important stages of its life cycle.
title_full Gene fitness landscapes of Vibrio cholerae at important stages of its life cycle.
title_fullStr Gene fitness landscapes of Vibrio cholerae at important stages of its life cycle.
title_full_unstemmed Gene fitness landscapes of Vibrio cholerae at important stages of its life cycle.
title_short Gene fitness landscapes of Vibrio cholerae at important stages of its life cycle.
title_sort gene fitness landscapes of vibrio cholerae at important stages of its life cycle
url https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1003800&type=printable
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AT davidwlazinski genefitnesslandscapesofvibriocholeraeatimportantstagesofitslifecycle
AT faithwallacegadsden genefitnesslandscapesofvibriocholeraeatimportantstagesofitslifecycle
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