Variation in Salmonella enterica Serovar Typhi IncHI1 Plasmids during the Global Spread of Resistant Typhoid Fever |
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| Authors: | 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 |
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| Affiliation: | The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom,1. Centre for Molecular Microbiology and Infection, Imperial College, London, United Kingdom,2. Bacterial Microarray Group, Department of Medical Microbiology, St Georges Hospital Medical School, London, United Kingdom,3. Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire, United Kingdom,4. Aga Khan University Medical Centre, Karachi, Pakistan5. |
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| 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. |
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