Investigating biological functions of the staphylococcal type VII secretion systems

Lead Research Organisation: University of Warwick
Department Name: School of Life Sciences

Abstract

Staphylococcus aureus is a leading cause of infections in animals and humans. Staphylococcal infections ranging from skin abscesses to septic shock have placed a huge financial burden on healthcare systems around the world. Antibiotic-resistant strains such as methicillin-resistant S.aureus (MRSA) and recurrent infections have made treatment of staphylococcal infections challenging. In animals, S.aureus causes mastitis, a severe infection of the mammary glands in dairy cows and is responsible for 10%-20% of the clinical and subclinical mastitis cases studied. Clinical mastitis impacts the health and welfare of dairy animals, and can cause death in worst cases. Persistent sub clinical infections are hard to eradicate.

S.aureus encodes a specialised type VII Esat-6 secretion system (Ess), a system that was originally described in the intracellular pathogen, Mycobacterium tuberculosis. The staphylococcal Ess encodes virulence factors required for staphylococcal virulence and persistence in murine staphylococcal infection models. The Ess proteins are considered excellent vaccine and drug targets. The molecular mechanisms underlying Ess functions and its role in mediating persistent staphylococcal infection remain unclear.

The goal of this project is to understand mechanisms by which Ess proteins mediate host and inter-bacterial interactions during staphylococcal infection. Employing isogenic mutants, the roles of individual Ess components will be investigated using global transcriptomic, proteomic and lipidomic approaches. In vitro cell infection assays will be used to study host cellular pathways that are modulated by Ess proteins. To understand the functions of Ess during staphylococcal infection, Ess-associated local immune and cellular responses will be studied in murine models of acute and chronic infection. Deciphering the biological roles of the Ess proteins will contribute to our understanding of staphylococcal mechanisms of persistence during infection.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/M01116X/1 01/10/2015 30/09/2023
2097375 Studentship BB/M01116X/1 01/10/2018 30/09/2022 Victoria Smith