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

Canals, Rocio (författare)
Univ Liverpool, Inst Integrat Biol, Liverpool, Merseyside, England
Larsson, Disa (författare)
Uppsala universitet,Mikrobiologi,Univ Liverpool, Inst Integrat Biol, Liverpool, Merseyside, England
Kroger, Carsten (författare)
Univ Liverpool, Inst Integrat Biol, Liverpool, Merseyside, England; Trinity Coll Dublin, Moyne Inst Prevent Med, Sch Genet & Microbiol, Dept Microbiol, Dublin, Ireland
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Owen, Sian V. (författare)
Univ Liverpool, Inst Integrat Biol, Liverpool, Merseyside, England; Harvard Med Sch, Dept Biomed Informat, Boston, MA USA
Fong, Wai Yee (författare)
Univ Liverpool, Inst Integrat Biol, Liverpool, Merseyside, England
Lacharme-Lora, Lizeth (författare)
Univ Liverpool, Inst Integrat Biol, Liverpool, Merseyside, England
Zhu, Xiaojun (författare)
Univ Liverpool, Inst Integrat Biol, Liverpool, Merseyside, England
Wenner, Nicolas (författare)
Univ Liverpool, Inst Integrat Biol, Liverpool, Merseyside, England
Carden, Sarah E. (författare)
Stanford Univ, Dept Microbiol & Immunol, Sch Med, Stanford, CA USA
Honeycutt, Jared (författare)
Stanford Univ, Dept Microbiol & Immunol, Sch Med, Stanford, CA USA
Monack, Denise M. (författare)
Stanford Univ, Dept Microbiol & Immunol, Sch Med, Stanford, CA USA
Kingsley, Robert A. (författare)
Quadram Inst Biosci, Norwich Res Pk, Norwich, Norfolk, England
Brownridge, Philip (författare)
Univ Liverpool, Inst Integrat Biol, Liverpool, Merseyside, England
Chaudhuri, Roy R. (författare)
Univ Sheffield, Dept Mol Biol & Biotechnol, Sheffield, S Yorkshire, England
Rowe, Will P. M. (författare)
Univ Liverpool, Inst Integrat Biol, Liverpool, Merseyside, England; STFC Daresbury Lab, Dept Comp Sci, Warrington, Cheshire, England
Predeus, Alexander V. (författare)
Univ Liverpool, Inst Integrat Biol, Liverpool, Merseyside, England
Hokamp, Karsten (författare)
Trinity Coll Dublin, Smurfit Inst Genet, Sch Genet & Microbiol, Dept Genet, Dublin, Ireland
Gordon, Melita A. (författare)
Univ Liverpool, Inst Infect & Global Hlth, Liverpool, Merseyside, England; Univ Malawi, Coll Med, Malawi Liverpool Wellcome Trust Clin Res Programm, Zomba, Malawi
Hinton, Jay C. D. (författare)
Univ Liverpool, Inst Integrat Biol, Liverpool, Merseyside, England
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 (creator_code:org_t)
2019-01-15
2019
Engelska.
Ingår i: PLoS biology. - : PUBLIC LIBRARY SCIENCE. - 1544-9173 .- 1545-7885. ; 17:1
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Infektionsmedicin (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Infectious Medicine (hsv//eng)

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