Global Health: Typhoid, Dysentery and Tuberculosis

  • Project Leader

    Dr Kathryn Holt
    T: +61 03 9035 3155
    E: kholt@unimelb.edu.au
    W: Personal web page

    Location: Centre for Systems Genomics, Building 184 (Old Microbiology), Royal Pde, Parkville

Project Details

Typhoid fever and dysentery are enteric infections, caused by the ingestion of Salmonella or Shigella bacteria that are pathogenic to humans. There are >25 million cases every year of typhoid fever and >150 million of dysentery, mostly in developing countries where there is limited access to clean water.

Both pathogens are highly monomorphic, meaning that they have evolved recently and have relatively low levels of genetic variation in their populations to facilitate typing and tracking. Therefore to study the evolution and transmission of typhoid and dysentery, we use whole genome sequencing. The genome data is subjected to phylogenetic analysis (to track transmission) and comparative genome analysis (to investigate evolution and the emergence of drug resistance).

Where possible, we couple this with spatiotemporal (where and when the bacteria were isolated) information in order to trace the evolution and spread of the bacteria through space and time. This can be done at the global level (to investigate the spread of Typhi and Shigella across continents) or at the local level (to investigate transmission of the infections within individual cities or countries) and can be used to date transmission events. These studies are mostly done in collaboration with Stephen Baker (Oxford University Clinical Research Unit, Vietnam) and Gordon Dougan and Nick Thomson (Wellcome Trust Sanger Institute, Cambridge).

Recent publications:

* Genomic analysis of diversity, population structure, virulence, and antimicrobial resistance in Klebsiella pneumoniae, an urgent threat to public health (page contains a link to the paper in PNAS, 2015)

* Phylogeographical analysis of the dominant multidrug-resistant H58 clade of SalmonellaTyphi identifies inter- and intracontinental transmission events (page contains a link to the paper Nature Genetics, 2015)

*Shigella sonnei genome sequencing and phylogenetic analysis indicate recent global dissemination from Europe (page contains a link to the paper in Nature Genetics, 2012)

Tracking the establishment of local endemic populations of an emergent enteric pathogen (page contains link to the paper in PNAS, 2013)

Collaborators

  • Stephen Baker (Oxford University Clinical Research Unit, Vietnam)
  • Nick Thomson (Wellcome Trust Sanger Institute, Cambridge)
  • Gordon Dougan (University of Cambridge, Wellcome Trust Sanger Institute, Cambridge)
  • Sarah Dunstan (Peter Doherty Institute)
  • YY Teo (National University of Singapore)

Research Group

Holt Laboratory: Pathogen Genomics and Bioinformatics



Faculty Research Themes

Infection and Immunology

School Research Themes

Infection & Immunity, Systems Biology



Key Contact

For further information about this research, please contact the research group leader.

Department / Centre

Biochemistry and Molecular Biology