JB Accepts, published online ahead of print on 23 March 2007

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J. Bacteriol. doi:10.1128/JB.00232-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Multidrug-resistant Salmonella enterica serovar Paratyphi A harbour IncHI1 plasmids similar to those found in serovar Typhi

Kathryn E. Holt, Nicholas R. Thomson, John Wain, Minh Duy Phan, Satheesh Nair, Rumina Hasan, Zulfiqar A. Bhutta, Michael A. Quail, Halina Norbertczak, Danielle Walker, Gordon Dougan, and Julian Parkhill^*

Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK; Aga Khan University, Karachi, Pakistan

^* To whom correspondence should be addressed. Email: parkhill{at}sanger.ac.uk.

Salmonella enterica serovars Typhi and Paratyphi A (S. Typhi and S. Paratyphi A respectively) both cause systemic infections in humans which are referred to as enteric fever. Multiple drug resistant (MDR) S. Typhi isolates emerged in the 1980's and in recent years MDR S. Paratyphi A infections have become established as a significant problem across Asia. MDR in S. Typhi is almost invariably associated with IncHI1 plasmids but the genetic basis of MDR in S. Paratyphi A has remained predominantly undefined. The DNA sequence of an IncHI1 plasmid, pAKU_1, encoding MDR in a S. Paratyphi A strain has been determined. Significantly, this plasmid shares a common IncHI1-associated DNA backbone with the S. Typhi plasmid pHCM1 and a Salmonella enterica serovar Typhimurium plasmid pR27. pAKU_1 and pHCM1 share 14 antibiotic resistance genes encoded within similar mobile elements, which appear to form a 24kb composite transposon that has transferred as a single unit into different positions into their IncHI1 backbones. Thus these plasmids have acquired similar antibiotic resistance genes independently via the horizontal transfer of mobile DNA elements. Furthermore two IncHI1 plasmids from Vietnamese S. Typhi were found to contain features of the backbone sequence of pAKU_1 rather than pHCM1, with the composite transposon inserted in the same location as in the pAKU_1 sequence. Our data shows that these S. Typhi and Paratyphi A IncHI1 plasmids share highly conserved core DNA and have acquired similar mobile elements encoding antibiotic resistance genes in the past decades.

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