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Emergence of a globally dominant IncHI1 plasmid type associated with multiple drug resistant typhoid

Kathryn E Holt1, Minh Duy Phan, Stephen Baker

  • 1Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom. kholt@unimelb.edu.au

Plos Neglected Tropical Diseases
|August 4, 2011
PubMed

Insights

Multi-drug resistant Salmonella Typhi (S. Typhi) is a global threat. A dominant clone, S. Typhi H58 with the IncHI1 PST6 plasmid, emerged in 1995, conferring a salt-growth advantage via the BetU gene.

Area of Science:

  • Microbiology
  • Genetics
  • Epidemiology

Background:

  • Typhoid fever, caused by Salmonella enterica serovar Typhi (S. Typhi), is a significant global health issue.
  • Multi-drug resistant (MDR) S. Typhi strains, primarily carrying IncHI1 plasmids, have become prevalent since the 1970s.
  • Understanding the evolution and spread of MDR S. Typhi is crucial for public health.

Purpose of the Study:

  • To investigate the evolutionary history and genetic diversity of IncHI1 plasmids in S. Typhi.
  • To identify factors contributing to the global spread of a dominant MDR S. Typhi clone.
  • To determine if specific IncHI1 plasmid types confer a selective advantage.

Main Methods:

  • Genotyping of over 300 single nucleotide polymorphisms (SNPs) in conserved regions of IncHI1 plasmids.
  • Analysis of plasmid and chromosomal SNPs in over 450 S. Typhi isolates from 1958 onwards.
  • Phenotypic analysis comparing the growth of S. Typhi strains with different IncHI1 plasmids (PST6 vs. PST1) in various conditions.

Main Results:

  • Prior to 1995, diverse IncHI1 plasmid types circulated in distinct S. Typhi haplotypes, with evidence of plasmid transfer.
  • From 1995, a dominant MDR clone emerged, characterized by S. Typhi haplotype H58 and IncHI1 plasmid sequence type 6 (PST6), accounting for 98% of MDR isolates.
  • The IncHI1 PST6 plasmid, unlike PST1, conferred the ability to grow in high salt (4.7% NaCl) due to the Tn6062 transposon encoding BetU.

Conclusions:

  • The emergence of the S. Typhi H58/PST6 clone since 1995 has led to the global spread of MDR typhoid fever.
  • The BetU gene within the Tn6062 transposon on the PST6 plasmid likely provides a selective advantage in high-salt environments.
  • This study highlights the importance of plasmid evolution in driving the epidemiology of infectious diseases.

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