According to the World Health Organization, if effective intervention methods against antimicrobial resistance are not made, 10 million deaths could occur annually by 2050. Furthermore, no new family of antibiotics has been commercialized in the past 25 years.
How do antibiotics work? An antibiotic is a natural or synthetic substance that destroys or blocks bacterial propagation. The first case can be qualified as a bactericidal antibiotic and the second one, as a bacteriostatic antibiotic. Antibiotics were introduced into our daily lives after World War II. They are considered as one of the biggest therapeutic advances of the 20thcentury. As a matter of fact, antibiotics managed to increase our life expectancy for more than 10 years. However, the overuse or misuse of certain antibiotics conducted to a phenomenon called antimicrobial resistance, meaning that the antibiotic loses its ability to treatthe bacterial infection. In hospitals, for example, this resistance leads to an increase in nosocomial infections due to particularly resistant germs such as Escherichia coli. According to the Health Minister, nosocomialinfections cause 4 000 deaths per year in France.
Since this phenomenon cannot continue to persist and antibiotics are not the solution anymore, we wish to exploit the power of synthetic biology in order to face this nasty resistance.
With the help of synthetic biology, the iGEM IONIS 2020 Team advances an alternative to antibiotics to fight against pathogenic bacteria, especially those which are resistant to antibiotics. Synthetic biology is defined as in vitro DNA synthesis and together with biology and bioinformatics, synthetic biology aims to rethink and redesign living systems.
To face this major health issue, we conceived the project BacTail. BacTail is inspired by certain characteristics of bacteriophages which are defined as bacterial viruses. It is composed of a capsid containing the bacteriophage’s genome, a more or less long sheath, and caudal fibers which are the LTFs. The project aims at using specific genetic sequences coding for Long Tail Fibers (LTFs) from bacteriophages allowing them to recognize and, later on, lyse specific bacteria.
Sup’Biotech students of the 2020 iGEM IONIS team will use LTFs coming from bacteriophages of the Myoviridaefamily. The aim is to express them on the surface of Escherichi coli(E. coli) so that they can specifically recognize, attack and kill pathogenic bacteria, that have developed antibiotic resistance.
Our proof of concept will be based on specific recognition of a target bacteria (mimicking the future pathogenic bacterium), which will be another strain of E. coli. This recognition will have to induce subsequent death of the targeted E. coli.
We have planned three main objectives in the BacTail project:
- Specific recognition of targeted bacteria by LTF
- Inducing attack to the targeted bacteria
- Death of our engineered bacteria after it had fulfilled its mission
Our team is also composed of four ESME Sudria students, who are specialized in informatics and electronics. Thanks to their help, a further aim is to create a database, that will help assembling the key components to be integrated in our engineered model. This modularity will allow our system to have a specific response to any particular organism.