Variation in Salmonella enterica Serovar Typhi IncHI1 Plasmids during the Global Spread of Resistant Typhoid Fever

Minh-Duy Phan, Claire Kidgell, Satheesh Nair, Kathryn E. Holt, Arthur K. Turner, Jason Hinds, Philip Butcher, Fiona J. Cooke, Nicholas R. Thomson, Richard Titball, Zulfiqar A. Bhutta, Rumina Hasan, Gordon Dougan, John Wain

Research output: Contribution to journalArticlepeer-review

70 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)716-727
Number of pages12
JournalAntimicrobial Agents and Chemotherapy
Volume53
Issue number2
DOIs
Publication statusPublished - Feb 2009

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