Typhoid fever: novel cellular mechanisms driving host defence

Year of award: 2015


  • Dr Stefania Spano

    University of Aberdeen

Project summary

Typhoid fever is caused by Salmonella enterica serovar Typhi (S. Typhi), a unique intracellular pathogen that only infects humans. The molecular mechanisms underlying this host specificity are still poorly understood. I have identified a novel trafficking pathway that blocks S. Typhi survival in macrophages from non-susceptible hosts, such as mice. This pathway, which depends on Rab32 GTPase, is emerging as a general antimicrobial pathway critical for killing intracellular pathogens. The differences in this pathway between mice and humans may underpin the successful infection of humans by S. Typhi. My preliminary data, backed by genome-wide association studies, suggest that this pathway is active in humans but there must be substantial differences to account for the different host susceptibilities.

The objectives of this project are to determine the role of the Rab32 antimicrobial pathway in controlling pathogen growth in humans and elucidate the mechanisms that kill S. Typhi in human macrophages.

These studies will empower a larger study to identify novel S. Typhi virulence factors and to suggest ways to boost innate immunity pathways to control bacterial diseases.