title: Variation in Salmonella enterica serovar typhi IncHI1 plasmids during the global spread of resistant typhoid fever.
abstract: A global collection of plasmids of the IncHI1 incompatibility group from Salmonella enterica serovar Typhi were analyzed by using a combination of DNA sequencing, DNA sequence analysis, PCR, and microarrays. The IncHI1 resistance plasmids of serovar Typhi display a backbone of conserved gene content and arrangement, within which are embedded preferred acquisition sites for horizontal DNA transfer events. The variable regions appear to be preferred acquisition sites for DNA, most likely through composite transposition, which is presumably driven by the acquisition of resistance genes. Plasmid multilocus sequence typing, a molecular typing method for IncHI1 plasmids, was developed using variation in six conserved loci to trace the spread of these plasmids and to elucidate their evolutionary relationships. The application of this method to a collection of 36 IncHI1 plasmids revealed a chronological clustering of plasmids despite their difference in geographical origins. Our findings suggest that the predominant plasmid types present after 1993 have not evolved directly from the earlier predominant plasmid type but have displaced them. We propose that antibiotic selection acts to maintain resistance genes on the plasmid, but there is also competition between plasmids encoding the same resistance phenotype.
authors.affiliation: The Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom.
authors.forename: Minh-Duy
authors.initials: MD
authors.lastname: Phan
authors.forename: Claire
authors.initials: C
authors.lastname: Kidgell
authors.forename: Satheesh
authors.initials: S
authors.lastname: Nair
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Holt
authors.forename: Arthur K
authors.initials: AK
authors.lastname: Turner
authors.forename: Jason
authors.initials: J
authors.lastname: Hinds
authors.forename: Philip
authors.initials: P
authors.lastname: Butcher
authors.forename: Fiona J
authors.initials: FJ
authors.lastname: Cooke
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Thomson
authors.forename: Richard
authors.initials: R
authors.lastname: Titball
authors.forename: Zulfiqar A
authors.initials: ZA
authors.lastname: Bhutta
authors.forename: Rumina
authors.initials: R
authors.lastname: Hasan
authors.forename: Gordon
authors.initials: G
authors.lastname: Dougan
authors.forename: John
authors.initials: J
authors.lastname: Wain
mesh_terms: D004269:DNA, Bacterial / Q000235:genetics; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D010957:Plasmids / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012485:Salmonella typhi / Q000235:genetics*; D014435:Typhoid Fever / Q000453:epidemiology* / Q000382:microbiology*; D014744:Vietnam / Q000453:epidemiology
chemical_list: D004269:DNA, Bacterial