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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Public Library of Science (PLoS)
2013-01-01
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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. |
format | Article |
id | doaj-art-f3d4b7a97a44454ea7a026a2aa7c8f73 |
institution | Kabale University |
issn | 1553-7366 1553-7374 |
language | English |
publishDate | 2013-01-01 |
publisher | Public Library of Science (PLoS) |
record_format | Article |
series | PLoS Pathogens |
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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