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Adding function to the genome of AfricanSalmonellaST313

Authors: Canals, Rocío; Hammarlöf, Disa; Kröger, Carsten; Owen, Siân; Fong, Wai Yee; Lacharme-Lora, Lizeth; Zhu, Xiaojun; +12 Authors

Adding function to the genome of AfricanSalmonellaST313

Abstract

Salmonella Typhimurium ST313 causes invasive nontyphoidal Salmonella (iNTS) disease in sub-Saharan Africa, targeting susceptible HIV + , malarial or malnourished individuals. An in-depth genomic comparison between the ST313 isolate D23580, and the well-characterized ST19 isolate 4/74 that causes gastroenteritis across the globe, revealed extensive synteny. To understand how the 856 nucleotide variations generated phenotypic differences, we devised a large-scale experimental approach that involved the global gene expression analysis of strains D23580 and 4/74 grown in sixteen infection-relevant growth conditions. Comparison of transcriptional patterns identified virulence and metabolic genes that were differentially expressed between D23580 versus 4/74, many of which were validated by proteomics. We also uncovered the S. Typhimurium D23580 and 4/74 genes that showed expression differences during infection of murine macrophages. Our comparative transcriptomic data are presented in a new enhanced version of the Salmonella expression compendium SalComD23580: bioinf.gen.tcd.ie/cgi-bin/salcom_v2.pl . We discovered that the ablation of melibiose utilization was caused by 3 independent SNP mutations in D23580 that are shared across ST313 lineage 2, suggesting that the ability to catabolise this carbon source has been negatively selected during ST313 evolution. The data revealed a novel plasmid maintenance system involving a plasmid-encoded CysS cysteinyl-tRNA synthetase, highlighting the power of large-scale comparative multi-condition analyses to pinpoint key phenotypic differences between bacterial pathovariants.

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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
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popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
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influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
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Funded by
SNSF| Characterization of novel prophage-encoded antisense RNAs of the human enteropathogenic bacterium Salmonella
Project
  • Funder: Swiss National Science Foundation (SNSF)
  • Project Code: 158684
  • Funding stream: Careers | Fellowships | Early Postdoc.Mobility
,
WT| Novel virulence properties of non-typhoidal Salmonella associated with epidemics of bloodstream infection.
Project
  • Funder: Wellcome Trust (WT)
  • Project Code: 106914
  • Funding stream: Pathogen Biology and Disease Transmission
iis
,
EC| DISTINCT
Project
DISTINCT
Determining how invasive S. Typhimurium infects human cells by transposon-insertion sequencing
  • Funder: European Commission (EC)
  • Project Code: 628450
  • Funding stream: FP7 | SP3 | PEOPLE
iis
,
UKRI| MicrobesNG: A scalable replicable biological sample repository incorporating whole-genome sequence data and analysis of thousands of microbial strains
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