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High-throughput Assay to Phenotype Salmonella enterica Typhimurium Association, Invasion, and Replication in Macrophages
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Multidrug-resistant Salmonella enterica serovar paratyphi A harbors IncHI1 plasmids similar to those found in serovar

Kathryn E Holt1, Nicholas R Thomson, John Wain

  • 1Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.

Journal of Bacteriology
|March 27, 2007
PubMed

Insights

Multidrug-resistant Salmonella Typhi and Paratyphi A infections are a growing concern. This study reveals that their resistance-conferring IncHI1 plasmids share a common DNA backbone and independently acquired similar antibiotic resistance genes.

Area of Science:

  • Microbiology
  • Genetics
  • Infectious Diseases

Background:

  • Salmonella enterica serovars Typhi and Paratyphi A cause enteric fever, a significant human systemic infection.
  • Multidrug resistance (MDR) in Salmonella Typhi is linked to IncHI1 plasmids, but the genetic basis for MDR in Salmonella Paratyphi A was largely unknown.
  • MDR Salmonella Paratyphi A infections are a growing public health problem, particularly in Asia.

Purpose of the Study:

  • To determine the genetic basis of multidrug resistance in Salmonella Paratyphi A by sequencing an IncHI1 plasmid.
  • To compare the genetic elements of Salmonella Paratyphi A IncHI1 plasmids with those found in Salmonella Typhi and Salmonella Typhimurium.

Main Methods:

  • DNA sequencing of the IncHI1 plasmid pAKU_1 from a multidrug-resistant Salmonella Paratyphi A strain.
  • Comparative genomic analysis of pAKU_1 with other IncHI1 plasmids, including pHCM1 (Salmonella Typhi) and pR27 (Salmonella Typhimurium).
  • Analysis of mobile genetic elements and antibiotic resistance genes within the plasmids.

Main Results:

  • The IncHI1 plasmid pAKU_1 confers multidrug resistance in Salmonella Paratyphi A.
  • pAKU_1 shares a conserved IncHI1 DNA backbone with Salmonella Typhi plasmid pHCM1 and Salmonella Typhimurium plasmid pR27.
  • Both pAKU_1 and pHCM1 contain 14 similar antibiotic resistance genes within a shared 24-kb composite transposon, acquired independently via horizontal gene transfer.
  • Two IncHI1 plasmids from Vietnamese Salmonella Typhi isolates showed backbone features similar to pAKU_1, with the composite transposon in the same location.

Conclusions:

  • Salmonella Typhi and Paratyphi A IncHI1 plasmids share a highly conserved core DNA.
  • Similar antibiotic resistance genes have been acquired independently by these plasmids through the horizontal transfer of mobile DNA elements.
  • This suggests convergent evolution in the acquisition of multidrug resistance in these important human pathogens.

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