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.

journal_name

PLoS Pathog

journal_title

PLoS pathogens

authors

Kamp HD,Patimalla-Dipali B,Lazinski DW,Wallace-Gadsden F,Camilli A

doi

10.1371/journal.ppat.1003800

subject

Has Abstract

pub_date

2013-01-01 00:00:00

pages

e1003800

issue

12

eissn

1553-7366

issn

1553-7374

pii

PPATHOGENS-D-13-02091

journal_volume

9

pub_type

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