title: Emergence of a globally dominant IncHI1 plasmid type associated with multiple drug resistant typhoid.
abstract: Typhoid fever, caused by Salmonella enterica serovar Typhi (S. Typhi), remains a serious global health concern. Since their emergence in the mid-1970s multi-drug resistant (MDR) S. Typhi now dominate drug sensitive equivalents in many regions. MDR in S. Typhi is almost exclusively conferred by self-transmissible IncHI1 plasmids carrying a suite of antimicrobial resistance genes. We identified over 300 single nucleotide polymorphisms (SNPs) within conserved regions of the IncHI1 plasmid, and genotyped both plasmid and chromosomal SNPs in over 450 S. Typhi dating back to 1958. Prior to 1995, a variety of IncHI1 plasmid types were detected in distinct S. Typhi haplotypes. Highly similar plasmids were detected in co-circulating S. Typhi haplotypes, indicative of plasmid transfer. In contrast, from 1995 onwards, 98% of MDR S. Typhi were plasmid sequence type 6 (PST6) and S. Typhi haplotype H58, indicating recent global spread of a dominant MDR clone. To investigate whether PST6 conferred a selective advantage compared to other IncHI1 plasmids, we used a phenotyping array to compare the impact of IncHI1 PST6 and PST1 plasmids in a common S. Typhi host. The PST6 plasmid conferred the ability to grow in high salt medium (4.7% NaCl), which we demonstrate is due to the presence in PST6 of the Tn6062 transposon encoding BetU.
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom. kholt@unimelb.edu.au
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Holt
authors.forename: Minh Duy
authors.initials: MD
authors.lastname: Phan
authors.forename: Stephen
authors.initials: S
authors.lastname: Baker
authors.forename: Pham Thanh
authors.initials: PT
authors.lastname: Duy
authors.forename: Tran Vu Thieu
authors.initials: TV
authors.lastname: Nga
authors.forename: Satheesh
authors.initials: S
authors.lastname: Nair
authors.forename: A Keith
authors.initials: AK
authors.lastname: Turner
authors.forename: Ciara
authors.initials: C
authors.lastname: Walsh
authors.forename: Séamus
authors.initials: S
authors.lastname: Fanning
authors.forename: Sinéad
authors.initials: S
authors.lastname: Farrell-Ward
authors.forename: Shanta
authors.initials: S
authors.lastname: Dutta
authors.forename: Sam
authors.initials: S
authors.lastname: Kariuki
authors.forename: François-Xavier
authors.initials: FX
authors.lastname: Weill
authors.forename: Julian
authors.initials: J
authors.lastname: Parkhill
authors.forename: Gordon
authors.initials: G
authors.lastname: Dougan
authors.forename: John
authors.initials: J
authors.lastname: Wain
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D004269:DNA, Bacterial / Q000235:genetics / Q000302:isolation & purification; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D006801:Humans; D008826:Microbial Sensitivity Tests; D010802:Phylogeny; D010957:Plasmids / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D012485:Salmonella typhi / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D017422:Sequence Analysis, DNA; D014435:Typhoid Fever / Q000188:drug therapy / Q000382:microbiology*
chemical_list: D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial