Project description
The role of the microenvironment in infectious disease outcome
There is a rapid increase in antibiotic resistance, necessitating the discovery of new drugs or strategies to control infectious diseases. Understanding the interplay between host and pathogen as well as the influence of the tissue microenvironment will help scientists discover new targets for intervention. The EU-funded SalPhagoHet project will use Salmonella enterica to study the immune properties of neutrophils and resident tissue macrophages in different environments. Using proteomics, scientists will determine key factors required for phagocytosis by these immune cells as well as pathogen responses. The results will unveil permissive niches where pathogens can survive and spread.
Objective
Infectious diseases represent a major threat to global human health today. Antibiotic misuse has induced rapid emergence of resistant bacteria and it is becoming increasingly challenging to identify new, efficient drugs. Novel control strategies are urgently required. This project intends to uncover key host immune factors determining the outcome of a bacterial infection with the aim to identify strategies to synergise with the immune system. Emerging evidence suggests that heterogeneous host-pathogen encounters play a key role in disease outcome. To investigate the role of distinct tissue microenvironments during infection, I will use Salmonella enterica to study the immune properties of neutrophils and resident tissue macrophages, previously shown to be non-permissive and permissive environments, respectively. Specifically, I will use a novel approach of phagosome isolation by fluorescence-activated cell sorting and will combine it with sensitive high-resolution mass spectrometry. With this state-of-the-art technology, I will identify key host factors required for phagosome formation by proteomics, which will provide relevant insights into the biology of two key professional phagocytes with important applications in infection biology and immunology. Secondly, I will analyse Salmonella responses to these host determinants using proteomics and stress-inducible promoter fusions to reporter genes. This will highlight key bacterial strategies for intracellular survival and thus novel antimicrobial targets. Finally, I will confirm the in vivo role of identified key factors using a murine infection model. This integrated approach, investigating the host and the pathogen, will be broadly applicable to study other important infectious diseases. This project will highlight specific host and pathogen responses with the aim to close permissive niches where suboptimal antimicrobial exposure allows pathogens to survive and spread.
Fields of science
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsproteomics
- natural sciencesbiological sciencesmicrobiologybacteriology
- medical and health scienceshealth sciencesinfectious diseases
- medical and health sciencesbasic medicineimmunology
- natural scienceschemical sciencesanalytical chemistrymass spectrometry
Keywords
Programme(s)
Funding Scheme
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinator
NE1 7RU Newcastle Upon Tyne
United Kingdom