Project description
How Shigella hides in immune cells
Shigella is a major cause of infectious diarrhoea, with resistance to antibiotics becoming increasingly prevalent. While it was previously understood that Shigella induced rapid cell death in immune cells, emerging evidence suggests that specific strains, such as Shigella sonnei, can persist intracellularly within macrophages and establish long-term infections. These persistent infections may lead to recurrent illness, ongoing transmission and greater antibiotic resistance. With the support of the Marie Skłodowska-Curie Actions programme, the PRISM project will investigate the mechanisms by which S. sonnei persists inside macrophages and delineate the role of the lipopolysaccharide coating, called the O-antigen, in immune evasion. Using stem cell-derived human immune cells and advanced molecular tools, the study aims to support better diagnostics and treatments.
Objective
Shigella is a human-adapted invasive pathogen and a high-priority antimicrobial resistance (AMR) threat, responsible for up to 165 million cases of bacillary dysentery and over 200,000 deaths annually. Emerging evidence shows that certain lineages of Shigella, including Shigella sonnei, can establish long-term infections in patients and animal models. Persistent infections are a significant public health threat, as they can cause recurrent disease manifestations. Persistent infections also complicate diagnosis, encourage transmission, and reduce the effectiveness of antibiotic treatments, promoting the emergence of AMR. My findings reveal that S. sonnei can survive within human macrophages, challenging the long-standing view that Shigella invariably induces rapid macrophage death. The S. sonnei O-antigen, a surface polysaccharide, contributes significantly to the establishment of persistent infections; however, the exact mechanisms by which S. sonnei persists remain unknown. Using infections of human-induced pluripotent stem cell-derived macrophages, I aim to (i) characterise the S. sonnei intra-macrophage persistent infection niche (I will identify where and how S. sonnei survives inside macrophages, and which host pathways are altered during long-term infection); and (ii) dissect the role of the O-antigen in promoting persistent infection (I will determine how the O-antigen affects bacterial survival in host macrophages and how it contributes to immune evasion). To meet these objectives, I will adopt a multidisciplinary approach, involving stem cell technologies, advanced imaging techniques, state-of-the-art gene expression profiling, gene knockout-based screenings, and targeted modification of bacterial surface polysaccharides. This project will deliver the first characterisation of persistent S. sonnei infection in macrophages, shedding light on the development of improved diagnostics, therapeutics, and prophylactic strategies to combat Shigella infections.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences health sciences public health epidemiology epidemics prevention
- medical and health sciences medical biotechnology cells technologies stem cells
- natural sciences biological sciences genetics RNA transcriptomes
- natural sciences biological sciences biochemistry biomolecules carbohydrates
- medical and health sciences basic medicine pharmacology and pharmacy drug resistance antibiotic resistance
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) HORIZON-MSCA-2025-PF
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WC2R 2LS London
United Kingdom
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