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Comprehensive Assignment of Roles for Salmonella Typhimurium Genes in Intestinal Colonization of Food-Producing Animals

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  • Roy R Chaudhuri
  • Eirwen Morgan
  • Sarah E Peters
  • Stephen J Pleasance
  • Debra L Hudson
  • Holly M Davies
  • Jinhong Wang
  • Pauline M van Diemen
  • Anthony M Buckley
  • Alison J Bowen
  • Gillian D Pullinger
  • Daniel J Turner
  • Gemma C Langridge
  • A Keith Turner
  • Julian Parkhill
  • Ian G Charles
  • Duncan J Maskell
  • Mark P Stevens

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    Rights statement: Copyright: © 2013 Chaudhuri et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

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http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1003456
Original languageEnglish
Article numbere1003456
Number of pages11
JournalPLoS Genetics
Volume9
Issue number4
DOIs
Publication statusPublished - Apr 2013

Abstract

Chickens, pigs, and cattle are key reservoirs of Salmonella enterica, a foodborne pathogen of worldwide importance. Though a decade has elapsed since publication of the first Salmonella genome, thousands of genes remain of hypothetical or unknown function, and the basis of colonization of reservoir hosts is ill-defined. Moreover, previous surveys of the role of Salmonella genes in vivo have focused on systemic virulence in murine typhoid models, and the genetic basis of intestinal persistence and thus zoonotic transmission have received little study. We therefore screened pools of random insertion mutants of S. enterica serovar Typhimurium in chickens, pigs, and cattle by transposon-directed insertion-site sequencing (TraDIS). The identity and relative fitness in each host of 7,702 mutants was simultaneously assigned by massively parallel sequencing of transposon-flanking regions. Phenotypes were assigned to 2,715 different genes, providing a phenotype-genotype map of unprecedented resolution. The data are self-consistent in that multiple independent mutations in a given gene or pathway were observed to exert a similar fitness cost. Phenotypes were further validated by screening defined null mutants in chickens. Our data indicate that a core set of genes is required for infection of all three host species, and smaller sets of genes may mediate persistence in specific hosts. By assigning roles to thousands of Salmonella genes in key reservoir hosts, our data facilitate systems approaches to understand pathogenesis and the rational design of novel cross-protective vaccines and inhibitors. Moreover, by simultaneously assigning the genotype and phenotype of over 90% of mutants screened in complex pools, our data establish TraDIS as a powerful tool to apply rich functional annotation to microbial genomes with minimal animal use.

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