Understanding how bacteria survive in human blood and serum
Research type
Research Study
Full title
Understanding how bacteria survive in human blood and serum
IRAS ID
350263
Contact name
Maisem Laabei
Contact email
Sponsor organisation
University of Bristol
Duration of Study in the UK
3 years, 0 months, 5 days
Research summary
Complement represents a core component of innate immunity, central in the host defence against infection. Staphylococcus aureus is a major human pathogen that is responsible for a wide range of diseases from superficial infection to life-threatening diseases such as bacteraemia and endocarditis. A key feature of S aureus pathogenicity is the possession of a sophisticated anti-complement virulence arsenal. However, the vast majority of complement evasins (CE) has been investigated in isolation, either as recombinant proteins or using surrogate hosts. As a result, no study has analysed the contribution of all CE as physiologically produced by the living organism. This lack of clarity hinders our understanding of S aureus pathogenicity and the development of therapeutic interventions to prevent or treat infection.
Objective 1 of this study is to determine the molecular features underpinning S aureus complement evasion. In order to do this, we will develop and optimise an ex vivo human blood sepsis model and determine the importance of known complement evasins in enhancing survival following infection of blood over a specific time period. Currently we are creating isogenic mutants of all known complement evasins in two genetic S. aureus backgrounds to use in this sepsis model.
Objective 2 will investigate the importance of complement evasins in preventing complement deposition in opsonophagocytosis models, using primary neutrophils and pooled human serum. Bacterial phagocytosis and survival will be compared between wild-type and mutant S aureus strains.
Objective 3 of this study will employ specific antibodies and chemical agents to inhibit a variety of immune functions in human blood that inhibit bacterial growth, providing essential information on key host factors required to eliminate S. aureus from human blood.
REC name
HSC REC B
REC reference
25/NI/0035
Date of REC Opinion
27 Mar 2025
REC opinion
Further Information Favourable Opinion