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: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- natural sciencesbiological sciencesmicrobiologybacteriology
- natural sciencesbiological sciencesmicrobiologyvirology
- natural sciencesbiological sciencesbiochemistrybiomolecules
- medical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsantibiotics
You need to log in or register to use this function
We are sorry... an unexpected error occurred during execution.
You need to be authenticated. Your session might have expired.
Thank you for your feedback. You will soon receive an email to confirm the submission. If you have selected to be notified about the reporting status, you will also be contacted when the reporting status will change.
Keywords
Programme(s)
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Funding Scheme
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European FellowshipsCoordinator
08002 Barcelona
Spain