Project description
Engineered commensal bacteria for antimicrobial delivery
Staphylococcus aureus is a leading cause of skin infections, ranging from mild lesions to life-threatening conditions. S. aureus is known for its invasiveness and high antibiotic resistance, presenting a major public health issue. Antimicrobial peptides (AMPs) are widely encountered in nature and show promise as alternatives to antibiotics. However, their clinical use has been so far limited, in part because of their instability. With the support of the Marie Skłodowska-Curie Actions programme, the CuteAMP project proposes to engineer the dominant skin commensal bacterium Cutibacterium acnes to produce AMPs against S. aureus. Researchers will employ a linear plasmid to ensure temporary AMP production. For safety reasons, the plasmid will be programmed to degrade and the engineered bacteria to revert to their wild-type state.
Objective
Our skin is colonized by a myriad of bacteria, fungi and viruses that are collectively called the skin microbiota. The most common and consequential bacterial skin pathogen in humans is Staphylococcus aureus. It is an invasive pathogen responsible for varied ailments that commonly evolves resistance to antibiotics. Antimicrobial peptides (AMPs) have drawn interest from the scientific community because they are less prone to resistance development. However, they typically require complex formulations to enhance their half-life due to low stability, which decrease their efficiencies when topically applied.
I propose to genetically engineer Cutibacterium acnes, one of the most prevalent and abundant commensal microbes of the human skin, to produce AMPs for the treatment of S. aureus-associated skin infections. For this, I will develop a novel expression platform based on a synthetic linear plasmid with features of bacterial telomeres that will be progressively degraded after a limited number of replication cycles. I will also screen AMPs for their potency and specificity against S. aureus and the best candidates will be encoded on the linear plasmid.
The use of the linear plasmid as a platform of AMPs production will (i) ensure that the delivery of the AMP is limited in time to prevent the development of antibiotic resistance, and (ii) provide a stringent biocontainment of the modified bacteria, as engineered cells eventually revert to their wild-type genotype upon programmed plasmid loss. This project merges my expertise in synthetic biology and biochemistry with that of the host in engineering the skin microbiota. The linear plasmid with pre-programmed degradation will be a foundational tool for future engineering of commensal bacteria as live therapeutics. It will also represent a paradigm shift in biocontainment for genetically engineered organisms, that will hopefully bring the use of engineered skin bacteria for microbiome-based therapy a step closer to reality
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.
- natural sciences biological sciences synthetic biology
- natural sciences biological sciences biochemistry biomolecules
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs antibiotics
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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)
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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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(opens in new window) HORIZON-MSCA-2024-PF-01
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08002 Barcelona
Spain
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