According to the World Health Organization, if effective intervention methods against antimicrobial resistance are not conducted by 2050, 10 million deaths could occur annually. Note that 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 by 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 treat the 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, nosocomial infections cause 4 000 deaths per year in France.
Since this phenomenon cannot continue to persist and antibiotics are showing weaknesses, we wish to exploit the power of synthetic biology in order to face this nasty antimicrobial 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. Together with biology and bioinformatics, synthetic biology aims to rethink and redesign living systems.
To face this major healthcare issue, we conceived the project BacTail.
BacTail is inspired by certain characteristics of bacteriophages which are the natural predators of bacteria. They are composed of a capsid containing the bacteriophage’s genome, a more or less long sheath, and Long Tail Fibers (LTF). The project aims at using specific genetic sequences coding for Long Tail Fibers from bacteriophages allowing them to specifically recognize their target bacterium.
Sup’Biotech students of the 2020 iGEM IONIS team will use LTFs coming from bacteriophages of the Myoviridae family. The aim is to express them on the surface of Escherichi coli (E. coli) so that is it capable of specifically recognizing, attacking and killing 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 induce the death of the targeted E. coli.
We have planned three main objectives in the BacTail project:
- Specific recognition and binding of targeted bacteria by the LTF
- Induction of the attack of the targeted bacteria through the secretion of antimicrobial peptides that are toxic for the target
- Death of our engineered bacteria once it has fulfilled its mission, in order to avoid its propagation
Our team is also composed of 3 ESME Sudria students studying general engineering. Thanks to their help, we are developing a software that will help with the assembly of the key recognition components that must be integrated in our engineered model for it to recognize the target. This modularity will allow our system to have a specific response to any type of bacterial target. In addition, 2 students (from ESME and Epita, engineering school in computer science) are in charge of programming our wiki, which is a website that contains our entire project, for the iGEM competition.