ArticleBMC genomics2019
Retrospective application of transposon-directed insertion-site sequencing to investigate niche-specific virulence of Salmonella Typhimurium in cattle.
Article in BMC genomics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 17 citations in OpenAlex.
- The advantage of intergenic regions as genomic features for machine-learning-based host attribution ofMicrobial genomics · 2023Article
- Cross-species RNA-seq for deciphering host-microbe interactions.Nature reviews. Genetics · 2021Review
- Comparative genome analysis of Salmonella enterica serovar Gallinarum biovars Pullorum and Gallinarum decodes strain specific genes.PloS one · 2021Article
- A decade of advances in transposon-insertion sequencing.Nature reviews. Genetics · 2020Review
- AlbaTraDIS: Comparative analysis of large datasets from parallel transposon mutagenesis experiments.PLoS computational biology · 2020Article
- Metabolic and genetic basis for auxotrophies in Gram-negative species.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- The SNAP hypothesis: Chromosomal rearrangements could emerge from positive Selection during Niche Adaptation.PLoS genetics · 2020Article
- Nature and consequences of interactions between Salmonella enterica serovar Dublin and host cells in cattle.Veterinary research · 2019Article
- The fitness landscape of the African Salmonella Typhimurium ST313 strain D23580 reveals unique properties of the pBT1 plasmid.PLoS pathogens · 2019Article
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundSalmonella enterica subspecies enterica is an animal and zoonotic pathogen of global importance. Cattle are a significant reservoir of human non-typhoidal salmonellosis and can suffer enteric and systemic disease owing to the ability of Salmonella to survive within the bovine lymphatic system and intestines. Contamination of food can occur due to the incorporation of contaminated peripheral lymph nodes or by direct contamination of carcasses with gut contents. It is essential to understand the mechanisms used by Salmonella to enter and persist within the bovine lymphatic system and how they differ from those required for intestinal colonization to minimize zoonotic infections.
resultsTransposon-directed insertion site sequencing (TraDIS) was applied to pools of mutants recovered from mesenteric lymph nodes (MLNs) draining the distal ileum of calves after oral inoculation with a library of 8550 random S. Typhimurium mini-Tn5Km2 mutants in pools of 475 mutants per calf. A total of 8315 mutants representing 2852 different genes were detected in MLNs and their in vivo fitness was calculated. Using the same improved algorithm for analysis of transposon-flanking sequences, the identity and phenotype of mutants recovered from the distal ileal mucosa of the same calves was also defined, enabling comparison with previously published data and of mutant phenotypes across the tissues. Phenotypes observed for the majority of mutants were highly significantly correlated in the two tissues. However, 32 genes were identified in which transposon insertions consistently resulted in differential fitness in the ileal wall and MLNs, suggesting niche-specific roles for these genes in pathogenesis. Defined null mutations affecting ptsN and spvC were confirmed to result in tissue-specific phenotypes in calves, thus validating the TraDIS dataset.
conclusionsThis validation of the role of thousands of Salmonella genes and identification of genes with niche-specific roles in a key target species will inform the design of control strategies for bovine salmonellosis and zoonotic infections, for which efficacious and cross-protective vaccines are currently lacking.
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