Yeast-based biosensors for the specific and accessible detection of pathogens and antimicrobial resistance
Early and specific detection of microbial infections is crucial for the containment of diseases and for reducing the dependence on the use of antibiotics. There is however a lack of reliable, cheap and easy to use detection methods for day-to-day monitoring of infection and antimicrobial resistances in samples from patients, animals and the environment. This deficinecy is critical for the abuse of antibiotics and the diffusion of antimicrobial resistance. The aim of this project is establishing a method based on yeast biosensors that can detect with high specificity pathogens from different sources to develop a new, fast and specific diagnostic tool for resistant pathogens. We will achieve this by joining together strong research groups on antimicrobial resistance, systems biology, and strain engineering at SINTEF, Chalmers University and National Medicines Institute. Particular focus will be given to the detection of ESBL or carbapenemase-producing strains belonging to the emerging ESKAPE group of resistant pathogens. The biosensor is developed using the yeast Saccharomyces cerevisiae as host, which will be engineered to express specific receptors able to recognise unique molecules produced by the pathogens. The ligand-receptor binding initiates a cascade mechanism that activates the genes for the production of a red pigment visible to the naked eye. Using the biosensors, we aim to identify molecular markers specific for resistant pathogen strains, to enable fast, easy and inexpensive point-of-use profiling of resistant pathogens.
- Geir Klinkenberg, SINTEF - Applied research, technology and innovation, Norway (Coordinator)
- Verena Siewers, Chalmers University of Technology, Sweden (Partner)
- Alicja Kuch, National Medicines Institute, Poland (Partner)
The diffusion of antimicrobial-resistant strains is a major worldwide problem that afflicts many nations and in particular low and medium-income countries. The most dangerous antimicrobial-resistant pathogens belong to the ESKAPE group (i.e. Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter species). The scope of this project is to develop a cellular biosensor based on the yeast Saccharomyces cerevisiae. These yeasts cells are modified to be able to express engineered receptors (GPCRs) that can detect the presence of specific peptides which are tightly connected to the presence of a specific pathogen. Upon recognition of these pathogen-identifier peptides, the receptor triggers a chemical reaction that culminates with the production of pigment visible to the naked eye. The presence of the red pigment is a clear indication that we are in the presence of a specimen infected by a carbapenemase-producing strain.