Team:Grenoble Alpes

PyoBuster - Design

Antibiotic resistances are one of the main global health problems worldwide. These resistances come from their massive use as a preventive and therapeutic treatment.

Map of the world presenting
Resistance of Pseudomonas aeruginosa to Carbapenems.
The Center for Disease, Dynamics Economics & Policy. ResistanceMap: Antibiotic resistance. 2020. Date accessed: Oct 19, 2020.

Pseudomonas aeruginosa accounts for one of the most problematic/threatening bacteria partly due to its ability to form a 3D protective extracellular matrix: a BIOFILM

P. aeruginosa causes many health problems essentially because of its biofilm such as nosocomial, wound or burn infections, otitis, etc.

Introducing PyoBusters biotreatment

Our engineered E. coli can sense P. aeruginosa’s biofilm employing its Quorum Sensing. In presence of this biofilm, E. coli's population grows which constitutively produces and accumulates therapeutics molecules stocked inside them. At a threshold, the bacteria will be lysed and will deliver the therapeutics molecules on the biofilm. These steps can be repeated until the total destruction of P. aeruginosa.

How does it work?

Survival system:

This system is focused on BHL sensing. This molecule will allow PyoBusters to sense the biofilm and induce its survival. If no BHL is sensed, our system won’t grow and die.

Delivery system:

The delivery system is an essential part of PyoBusters. This system is based on E. coli’s own quorum sensing molecule: AI-2. When it reaches a threshold population it will trigger the production of the lysis protein and allow therapeutic molecules to be released through the lysis of PyoBusters.

Therapeutic system:

The engineered E. coli will constitutively produce therapeutics molecules in its cytoplasm. Thanks to the delivery system, these molecules will be released and will act on the biofilm and directly kill P. aeruginosa.

P. aeruginosa can develop its biofilm in different environmental conditions. To test PyoBusters, the engineered E. coli, in different infection conditions, we developed our own testing bench.

Our testing bench controls three physical parameters: the temperature, the humidity, and the rotation per minute (rpm). Thus it can reproduce specific environments.

To facilitate biological experiments, our system is equipped with a fluorescence measurement module. Thus the investigator can program an experiment.

Thanks to a web interface, we can access the testing bench on any connected computer and make it possible to program an experiment, and follow its evolution both remotely.

Discover our fantastic Project Promotion Video!