Typhoid Fever: Novel Cellular Mechanisms driving Host Defense. (360G-Wellcome-109680_Z_15_Z)

£99,995

Typhoid fever is caused by Salmonella enterica serovar Typhi (S. Typhi), a unique intracellular pathogen that can infect only humans. The molecular mechanisms underlying this host-specificity are still poorly understood. My research takes advantage of a powerful combination of cutting-edge experimental approaches to explore the host-pathogen molecular interface. Using these approaches I identified a novel trafficking pathway that blocks S. Typhi survival in macrophages from non-susceptible hosts , e.g. mice. This pathway, which depends on the Rab32 GTPase, is emerging as a general antimicrobial pathway critical for killing intracellular pathogens. The differences in this pathway between mice and humans likely 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 thi s project are to: 1) determine the role of the Rab32 antimicrobial pathway in controlling pathogen growth in humans; and 2) elucidate the mechanisms that promote killing of 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.

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Grant Details

Amount Awarded 99995
Applicant Surname Spano
Approval Committee ERG5 Pathogen Biology and Disease Transmission
Award Date 2015-09-15T00:00:00+00:00
Financial Year 2014/15
Grant Programme: Title Seed Award in Science
Internal ID 109680/Z/15/Z
Lead Applicant Prof Stefania Spano
Partnership Value 99995
Planned Dates: End Date 2018-10-31T00:00:00+00:00
Planned Dates: Start Date 2016-01-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region Scotland