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Preprints, Working Papers, ... Year : 2019

Global phylogenomics of multidrug resistant Salmonella enterica serotype Kentucky ST198


Salmonella enterica serotype Kentucky (S. Kentucky) can be a common causative agent of salmonellosis, usually associated with consumption of contaminated poultry. Antimicrobial resistance (AMR) to multiple drugs, including ciprofloxacin, is an emerging problem within this serotype. We used whole-genome sequencing (WGS) to investigate the phylogenetic structure and AMR content of 121 S. Kentucky ST198 isolates from five continents. Population structure was inferred using phylogenomic analysis and whole genomes were compared to investigate changes in gene content, with a focus on acquired AMR genes. Our analysis showed that multidrug resistant (MDR) S. Kentucky isolates belonged to a single lineage, which we estimate emerged circa 1989 following the acquisition of the AMR-associated Salmonella genomic island 1 (variant SGI1-K) conferring resistance ampicillin, streptomycin, gentamicin, sulfamethoxazole, and tetracycline. Phylogeographic analysis indicates this clone emerged in Egypt before disseminating into Northern, Southern and Western Africa, then to the Middle East, Asia and the European Union. The MDR clone has since accumulated various substitution mutations in the quinolone resistance determining regions (QRDR) of DNA gyrase (gyrA) and DNA topoisomerase (parC), such that most strains carry three QRDR mutations which together confer resistance to ciprofloxacin. The majority of AMR genes in the S. Kentucky genomes were carried either on plasmids or SGI structures. Remarkably, each genome carried a different SGI1-K derivative structure; this variation could be attributed to IS26-mediated insertions and deletions, which appear to have hampered previous attempts to trace the clone's evolution using sub-WGS resolution approaches. Several different AMR plasmids were also identified, encoding resistance to chloramphenicol, third-generation cephalosporins, carbapenems, and/or azithromycin. These results indicate that most MDR S. Kentucky circulating globally result from the clonal expansion of a single lineage that acquired chromosomal AMR genes 30 years ago, and has continued to diversify and accumulate additional resistances to last-line oral antimicrobials.


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SKentucky_mgen_130319Revised.pdf (2.78 Mo) Télécharger le fichier
Supplementary_Table6_VirulenceGenes.pdf (281.55 Ko) Télécharger le fichier
Supplementary_Table_1_01022019.xlsx (46.67 Ko) Télécharger le fichier
Supplementary_Table_2_IncI1.xlsx (46.52 Ko) Télécharger le fichier
Supplementary_Table_3_IncI1Core.pdf (46.15 Ko) Télécharger le fichier
Supplementary_Table_4_onePatientSNPs.xlsx (32.6 Ko) Télécharger le fichier
Supplementary_Table_5_resistanceGeneAssociations.pdf (46.46 Ko) Télécharger le fichier
supplementary_figure10_virulenceGenes.pdf (2.59 Mo) Télécharger le fichier
supplementary_figure1_regressions.pdf (142.23 Ko) Télécharger le fichier
supplementary_figure2_dateRandomisations.pdf (99.88 Ko) Télécharger le fichier
supplementary_figure3_treeSGI26(1).pdf (1.98 Mo) Télécharger le fichier
supplementary_figure4_sgiTypes.pdf (1013.55 Ko) Télécharger le fichier
supplementary_figure5_IS26_againstTime.pdf (175.03 Ko) Télécharger le fichier
supplementary_figure6_plasmidReplicons.pdf (5.77 Ko) Télécharger le fichier
supplementary_figure7_IncI1plasmids_midpointRooted.pdf (225.18 Ko) Télécharger le fichier
supplementary_figure8_ndmDepth.pdf (243.63 Ko) Télécharger le fichier
supplementary_figure9_brig_comparison_181217.pdf (18.39 Mo) Télécharger le fichier

Dates and versions

pasteur-02079525 , version 1 (26-03-2019)





Jane Hawkey, Simon Le Hello, Benoît Doublet, Sophie Granier, Rene S Hendriksen, et al.. Global phylogenomics of multidrug resistant Salmonella enterica serotype Kentucky ST198. 2019. ⟨pasteur-02079525⟩
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