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Antimicrobial Agents and Chemotherapy, February 2009, p. 716-727, Vol. 53, No. 2
0066-4804/09/$08.00+0     doi:10.1128/AAC.00645-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Variation in Salmonella enterica Serovar Typhi IncHI1 Plasmids during the Global Spread of Resistant Typhoid Fever{triangledown} ,{dagger}

Minh-Duy Phan,1 Claire Kidgell,2 Satheesh Nair,1 Kathryn E. Holt,1 Arthur K. Turner,1 Jason Hinds,3 Philip Butcher,3 Fiona J. Cooke,1 Nicholas R. Thomson,1 Richard Titball,4,{ddagger} Zulfiqar A. Bhutta,5 Rumina Hasan,5 Gordon Dougan,1 and John Wain1*

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

Received 16 May 2008/ Returned for modification 22 July 2008/ Accepted 13 October 2008

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.

* Corresponding author. Present address: Laboratory of Gastrointestinal Pathogens, Gastrointestinal, Emerging and Zoonotic Infections, Centre for Infections, Health Protection Agency, Colindale, 61 Colindale Avenue, London NW9 5HT, United Kingdom. Phone: 44 (0) 2083 277117. E-mail: John.Wain{at}hpa.org.uk

{triangledown} Published ahead of print on 17 November 2008.

{dagger} Supplemental material for this article may be found at http://aac.asm.org/.

{ddagger} Present address: School of Biosciences, University of Exeter, Devon EX4 4QD, United Kingdom.

Antimicrobial Agents and Chemotherapy, February 2009, p. 716-727, Vol. 53, No. 2
0066-4804/09/$08.00+0     doi:10.1128/AAC.00645-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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  • Hawkey, P. M., Jones, A. M. (2009). The changing epidemiology of resistance. J Antimicrob Chemother 64: i3-i10 [Abstract] [Full Text]  
  • Bhutta, Z. A., Threlfall, J. (2009). Addressing the Global Disease Burden of Typhoid Fever. JAMA 302: 898-899 [Full Text]  
  • Taylor, D. E. (2009). Thermosensitive Nature of IncHI1 Plasmid Transfer. Antimicrob. Agents Chemother. 53: 2703-2703 [Full Text]  


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