Adding function to the genome of African Salmonella Typhimurium ST313 strain D23580.


Journal

PLoS biology
ISSN: 1545-7885
Titre abrégé: PLoS Biol
Pays: United States
ID NLM: 101183755

Informations de publication

Date de publication:
01 2019
Historique:
entrez: 16 1 2019
pubmed: 16 1 2019
medline: 5 11 2019
Statut: epublish

Résumé

Salmonella Typhimurium sequence type (ST) 313 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 16 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: http://bioinf.gen.tcd.ie/cgi-bin/salcom_v2.pl. We discovered that the ablation of melibiose utilization was caused by three independent SNP mutations in D23580 that are shared across ST313 lineage 2, suggesting that the ability to catabolize this carbon source has been negatively selected during ST313 evolution. The data revealed a novel, to our knowledge, plasmid maintenance system involving a plasmid-encoded CysS cysteinyl-tRNA synthetase, highlighting the power of large-scale comparative multicondition analyses to pinpoint key phenotypic differences between bacterial pathovariants.

Identifiants

pubmed: 30645593
doi: 10.1371/journal.pbio.3000059
pii: PBIOLOGY-D-18-00880
pmc: PMC6333337
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e3000059

Subventions

Organisme : Wellcome Trust
ID : 106914/Z/15/Z
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/L024209/1
Pays : United Kingdom

Déclaration de conflit d'intérêts

The authors have declared that no competing interests exist.

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Auteurs

Rocío Canals (R)

Institute of Integrative Biology, University of Liverpool, Liverpool, United Kingdom.

Disa L Hammarlöf (DL)

Institute of Integrative Biology, University of Liverpool, Liverpool, United Kingdom.

Carsten Kröger (C)

Institute of Integrative Biology, University of Liverpool, Liverpool, United Kingdom.

Siân V Owen (SV)

Institute of Integrative Biology, University of Liverpool, Liverpool, United Kingdom.

Wai Yee Fong (WY)

Institute of Integrative Biology, University of Liverpool, Liverpool, United Kingdom.

Lizeth Lacharme-Lora (L)

Institute of Integrative Biology, University of Liverpool, Liverpool, United Kingdom.

Xiaojun Zhu (X)

Institute of Integrative Biology, University of Liverpool, Liverpool, United Kingdom.

Nicolas Wenner (N)

Institute of Integrative Biology, University of Liverpool, Liverpool, United Kingdom.

Sarah E Carden (SE)

Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, United States of America.

Jared Honeycutt (J)

Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, United States of America.

Denise M Monack (DM)

Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, United States of America.

Robert A Kingsley (RA)

Quadram Institute Bioscience, Norwich Research Park, Norwich, United Kingdom.

Philip Brownridge (P)

Institute of Integrative Biology, University of Liverpool, Liverpool, United Kingdom.

Roy R Chaudhuri (RR)

Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield, United Kingdom.

Will P M Rowe (WPM)

Institute of Integrative Biology, University of Liverpool, Liverpool, United Kingdom.

Alexander V Predeus (AV)

Institute of Integrative Biology, University of Liverpool, Liverpool, United Kingdom.

Karsten Hokamp (K)

Department of Genetics, School of Genetics and Microbiology, Smurfit Institute of Genetics, Trinity College Dublin, Ireland.

Melita A Gordon (MA)

Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom.
Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Malawi, Central Africa.

Jay C D Hinton (JCD)

Institute of Integrative Biology, University of Liverpool, Liverpool, United Kingdom.

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