Gene Fitness Landscapes of Vibrio cholerae at Important Stages of Its Life Cycle

PLoS Pathogens

Bharathi Patimalla-Dipali¹  Andrew Camilli¹  Heather D. Kamp¹  David W. Lazinski¹  Faith Wallace-Gadsden¹ 

[1] Howard Hughes Medical Institute and Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts, United States of America

关键词: Vibrio cholerae;    Ponds;    Aquatic environments;    Rabbits;    Glycogens;    Cholera;    Small intestine;    Transposable elements;   

DOI  :  10.1371/journal.ppat.1003800

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY