Role of a single noncoding nucleotide in the evolution of an epidemic African clade of Salmonella

Research output: Contribution to journalArticlepeer-review

Authors

  • Disa L Hammarlöf
  • Carsten Kröger
  • Siân V Owen
  • Rocío Canals
  • Lizeth Lacharme-Lora
  • Nicolas Wenner
  • Paul Wigley
  • Karsten Hokamp
  • Nicholas A Feasey
  • Melita A Gordon
  • Jay C D Hinton

Colleges, School and Institutes

External organisations

  • Department of Cell and Molecular Biology, Uppsala University, 751 24 Uppsala, Sweden.
  • Department of Microbiology, School of Genetics and Microbiology, Moyne Institute of Preventive Medicine, Trinity College Dublin, Dublin 2, Ireland.
  • University of Liverpool
  • Institute of Microbiology and Infection, University of Birmingham, Birmingham B15 2TT, United Kingdom.
  • Department of Genetics, School of Genetics and Microbiology, Smurfit Institute of Genetics, Trinity College Dublin, University of Dublin, Dublin 2, Ireland.
  • Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre 3, Malawi, Central Africa.

Abstract

Salmonella enterica serovar Typhimurium ST313 is a relatively newly emerged sequence type that is causing a devastating epidemic of bloodstream infections across sub-Saharan Africa. Analysis of hundreds of Salmonella genomes has revealed that ST313 is closely related to the ST19 group of S Typhimurium that cause gastroenteritis across the world. The core genomes of ST313 and ST19 vary by only ∼1,000 SNPs. We hypothesized that the phenotypic differences that distinguish African Salmonella from ST19 are caused by certain SNPs that directly modulate the transcription of virulence genes. Here we identified 3,597 transcriptional start sites of the ST313 strain D23580, and searched for a gene-expression signature linked to pathogenesis of Salmonella We identified a SNP in the promoter of the pgtE gene that caused high expression of the PgtE virulence factor in African S. Typhimurium, increased the degradation of the factor B component of human complement, contributed to serum resistance, and modulated virulence in the chicken infection model. We propose that high levels of PgtE expression by African S Typhimurium ST313 promote bacterial survival and dissemination during human infection. Our finding of a functional role for an extragenic SNP shows that approaches used to deduce the evolution of virulence in bacterial pathogens should include a focus on noncoding regions of the genome.

Details

Original languageEnglish
Pages (from-to)E2614-E2623
JournalProceedings of the National Academy of Sciences of the United States of America
Volume115
Issue number11
Early online date27 Feb 2018
Publication statusPublished - 13 Mar 2018

Keywords

  • Salmonella, noncoding genome, transcriptomics, evolution of virulence, host adaptation