Comprehensive assignment of roles for Salmonella typhimurium genes in intestinal colonization of food-producing animals.
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...
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2013
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oai:doaj.org-article:7820bce80403457dbb9f2d7f151160b72021-11-18T06:19:44ZComprehensive assignment of roles for Salmonella typhimurium genes in intestinal colonization of food-producing animals.1553-73901553-740410.1371/journal.pgen.1003456https://doaj.org/article/7820bce80403457dbb9f2d7f151160b72013-04-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23637626/pdf/?tool=EBIhttps://doaj.org/toc/1553-7390https://doaj.org/toc/1553-7404Chickens, 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.Roy R ChaudhuriEirwen MorganSarah E PetersStephen J PleasanceDebra L HudsonHolly M DaviesJinhong WangPauline M van DiemenAnthony M BuckleyAlison J BowenGillian D PullingerDaniel J TurnerGemma C LangridgeA Keith TurnerJulian ParkhillIan G CharlesDuncan J MaskellMark P StevensPublic Library of Science (PLoS)articleGeneticsQH426-470ENPLoS Genetics, Vol 9, Iss 4, p e1003456 (2013) |
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DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Genetics QH426-470 |
| spellingShingle |
Genetics QH426-470 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 Comprehensive assignment of roles for Salmonella typhimurium genes in intestinal colonization of food-producing animals. |
| description |
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. |
| format |
article |
| author |
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 |
| author_facet |
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 |
| author_sort |
Roy R Chaudhuri |
| title |
Comprehensive assignment of roles for Salmonella typhimurium genes in intestinal colonization of food-producing animals. |
| title_short |
Comprehensive assignment of roles for Salmonella typhimurium genes in intestinal colonization of food-producing animals. |
| title_full |
Comprehensive assignment of roles for Salmonella typhimurium genes in intestinal colonization of food-producing animals. |
| title_fullStr |
Comprehensive assignment of roles for Salmonella typhimurium genes in intestinal colonization of food-producing animals. |
| title_full_unstemmed |
Comprehensive assignment of roles for Salmonella typhimurium genes in intestinal colonization of food-producing animals. |
| title_sort |
comprehensive assignment of roles for salmonella typhimurium genes in intestinal colonization of food-producing animals. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2013 |
| url |
https://doaj.org/article/7820bce80403457dbb9f2d7f151160b7 |
| work_keys_str_mv |
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| _version_ |
1718424487328743424 |