Adding function to the genome of African<i>Salmonella</i>ST313

Canals, Rocío ORCID: 0000-0001-7079-7690, Hammarlöf, Disa, Kröger, Carsten ORCID: 0000-0003-0461-1530, Owen, Siân ORCID: 0000-0001-5330-3177, Fong, Wai Yee, Lacharme-Lora, Lizeth, Zhu, Xiaojun, Wenner, Nicolas, Carden, Sarah, Honeycutt, Jared
et al (show 9 more authors) (2018) Adding function to the genome of African<i>Salmonella</i>ST313. [Preprint]

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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: . 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.

Item Type: Preprint
Uncontrolled Keywords: 3107 Microbiology, 3207 Medical Microbiology, 32 Biomedical and Clinical Sciences, 31 Biological Sciences, Infectious Diseases, Digestive Diseases, Emerging Infectious Diseases, Genetics, Biotechnology, HIV/AIDS, Biodefense, Foodborne Illness, Sexually Transmitted Infections, Human Genome, 2.1 Biological and endogenous factors, 2.2 Factors relating to the physical environment, 2 Aetiology, Infection, 3 Good Health and Well Being
Depositing User: Symplectic Admin
Date Deposited: 02 Jan 2020 16:41
Last Modified: 20 Jun 2024 22:41
DOI: 10.1101/450098
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