Global phylogenomics of multidrug resistant Salmonella enterica serotype Kentucky ST198

Abstract

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.

National Prevalence of Salmonella enterica Serotype Kentucky ST198 with High-Level Resistance to Ciprofloxacin and Extended-Spectrum Cephalosporins in China, 2013 to 2017

“…Recently, the convergence of these high-level resistances has been found in a single serotype of S. enterica , Kentucky, which largely limits clinical treatment strategies ( 3 ). Epidemiological studies by using multilocus sequence typing (MLST) reveal that ciprofloxacin-resistant (CIP r ) S. Kentucky is a single clone belonging to sequence type 198 (ST198).…”

“…Since then, this clone has been detected with high prevalence in Africa, the Middle East, and southern Asia, and it is widely disseminated to Europe and North America via travel-related infections ( 4 – 8 ). In addition, S. Kentucky is a foodborne pathogen, and domestic poultry has largely contributed to its global spread (most recently in South Asia and Europe) ( 3 ). S. Kentucky ST198 has been established in poultry in France, Poland, the United States, and Vietnam ( 3 , 7 – 11 ).…”

“…In addition, S. Kentucky is a foodborne pathogen, and domestic poultry has largely contributed to its global spread (most recently in South Asia and Europe) ( 3 ). S. Kentucky ST198 has been established in poultry in France, Poland, the United States, and Vietnam ( 3 , 7 – 11 ). In some cases, the clone is also detected in bovines ( 10 , 11 ).…”

“…To understand the origin and evolutionary trajectory, a recent study analyzed a global collection of multidrug-resistant (MDR) S . Kentucky isolates by using whole-genome sequencing (WGS) for the first time ( 3 ). The results show that all of MDR S .…”

“…The results show that all of MDR S . Kentucky isolates belonged to ST198, which is estimated to have emerged circa 1989 in Egypt following the acquisition of the antimicrobial resistance (AMR)-associated Salmonella genomic island 1 (SGI1), conferring resistance to ampicillin, streptomycin, gentamicin, sulfamethoxazole, and tetracycline ( 3 ). In the early 2000s, amino acid substitutions in the quinolone resistance-determining regions (QRDRs) of GyrA and ParC conferring high-level resistance to fluoroquinolones were accumulated in ST198, further facilitating its wide dissemination ( 5 ).…”