SalPhagoHet · Characterisation of permissive and non-permissive phagosome environments during Salmonella systemic infection
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2021-09-01 → 2023-08-31
- EU contribution
- €212,934
- Participants
- 1
- Scheme
- MSCA-IF
Lines connect the coordinator with its partners.
Results in brief
Characterisation of permissive and non-permissive phagosome environments during Salmonella systemic infection
The action “Characterisation of permissive and non-permissive phagosome environments during Salmonella systemic infection” looks at the interaction between pathogens and their hosts during bacterial infections. Infectious disease studies often overlook the complexity of immune responses. However, bacterial infections are characterized by complex interactions between pathogen and host. These interactions are disparate and allow some bacterial cells to survive attacks from the immune system. Additionally, it has been shown that some bacteria are protected from antibiotic treatment due to specific host factors surrounding them. The aim of this project is to highlight specific host and pathogen responses in order to identify conditions that allow pathogens to survive and spread and, ultimately, to close these permissive niches. Antibiotic resistance is a threat to global health. When a bacterium becomes resistant to several antibiotics, it can become very difficult to find a way to treat that specific infection. Additionally, the person infected can easily spread the same multi-drug resistant pathogen to other people. It is becoming increasingly challenging to identify new, efficient drugs and, therefore, novel control strategies to synergise with the immune system are urgently required. The aim of this action was to identify potential permissive conditions that allow pathogen survival and spread. Specific objectives of this Marie Skłodowska Curie Action (MSCA) have been to (a) develop a new approach of phagosome isolation by fluorescence-activated cell sorting and combine it with sensitive high-resolution mass spectrometry to determine host protein markers over the infection; (b) highlight key bacterial strategies for intracellular survival, potentially identifying novel antimicrobial targets.
Data: CORDIS, © European Union
Project 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.
Original text from CORDIS.
Participants
- UNIVERSITY OF NEWCASTLE UPON TYNE · Newcastle Upon TyneCoordinatorUnited Kingdom
Links
Data: CORDIS, © European Union