Noso Infections | Bioaster

Aim/Technological Description

BIOASTER has setup A baumannii animal models mimicking relevant clinical infections: pneumonia and bacteremia based on constituted a library of bioluminescent relevant clinical A. baumannii strains.

The use of bioluminescence imaging refines animal models, allowing infections to be monitored non-invasively and in real-time, reducing the number of animals required to carry out experiments and providing further information regarding the development of disease.
The efficacy assessment and safety of the new products/drug before they enter human clinical trials need the deployment of several in vitro and in vivo approaches. Preclinical models play a crucial step in the development of new therapeutics and vaccines assays and play critical translational roles prior to any clinical application.

Background

Acinetobacter baumannii, has emerged as one of the most troublesome pathogens for health care institutions globally. The World Health Organization (WHO) has ranked carbapenem- resistant A baumannii as a critical priority pathogen on its global priority list of antibiotic-resistant bacteria to guide drug research and development.

Two preclinical relevant infections models related to A. baumannii have been deployed: Pneumoniae and bacteremia. To achieve this goal, firstly a library of bioluminescent clinically relevant A. baumnnii strains have been constituted. In the second time, a preclinical A. baumannii infection model has been set up: Pneumoniae (intranasal infection) and Bacteremia (intravenous infection) combined with imaging tools based on bioluminescence in order to monitor bacterial infection/ dissemination and antibiotic/drug efficacy. This approach allowed to implement relevant models to monitor longitudinally infection and any drug candidate efficacy (interesting to go and see funders).

Evidence / Results

BIOASTER has achieved the following results:

Bioluminescent Carbapenem sensitive strain of A. baumannii that is validated in vitro and in vivo
Bioluminescent Carbapenem resistant strain of A. baumannii that is validated in vitro and in vivo
Improve the sensitivity of in vivo imaging to follow drug efficacy below the current limit of detection

Advantages

The use of bioluminescence technology allows to perform a longitudinal monitoring. The consequences is the reducing of animal number (this has a positive ethical impact: 3R) as well as a smaller quantity of product. The approach provides a simultaneous monitoring of the kinetic of infection (in real time) and optimization of treatment (by monitoring infection burden in target organ).

Potential Applications

Hospital-acquired infections are causing problems at hospital level and are having a growing financial impact. Mainly due to gram-positive bacteria, mainly A. baumannii. A. baumannii increasing, with more and more resistance.
There is a high need for a model enabling monitoring over time, with imaging targeted to Pharma company (large and smaller) which focuses on nosocomial A. baumannii infections (and ESKAPE in general).
In a drug discovery pipeline, such technology may be used at the end of lead- optimization (between lead-optimization and drug candidate declaration).

Outlook

The technology is ready to be implemented for partners’ and clients’ projects. The technology is currently ready to perform the evaluation of compounds and their efficacy.
To constantly improve its technology, BIOASTER will be happy to enter into collaboration to

Enlarge its library of clinically relevant strains having different resistances
Constantly improve the model to increase its representativity.
Customize the model to each partner specific questions and needs.