Pathogens, Immunity and Microbiota

RESEARCH SUMMARY

The PIMs (Pathogens, Immunity and Microbiota) team is expert in the study of bacterial resistance to the host immune system. We characterize on one hand, the effects of the immune response on pathogenic bacteria, and on the other hand we develop new strategies to combat bacterial infections.

As bacterial model, we study the virulence of Bacillus cereus (Bc) and its mechanisms of resistance to the host immune system (ie nitrogen and oxidative response, antimicrobial peptides). We also develop sensing elements that recognize bacterial biomarkers for diagnostic applications in food security. PIMs present research interests include detections of Bc in clinical and food samples, Campylobacter spp. in poultry meats and E. coli in contaminated water.

We develop innovative strategies to combat bacterial infections based on our knowledge and expertise on bacterial resistance to the host nitrogen immune response. We mainly focus on bacteria of the ESKAPE group (ie, S. aureus, K. pneumoniae, P. aeruginisa, E. coli) for which the WHO has recently pointed an alarming antibio-resistance issue.

Finally, we aim to characterize the impact of the microbiota on the modulation of the host response and the development of pathogen infectivity.

Taken together, based on our data, the projects of the team are divided into five axes:

1-Bacterial resistance to the host immune system

2-Diagnostic tools

3-Therapeutic innovation: new antibiotic strategy

4-Host / pathogen / microbiota

5-Public communication

Theme 1.- Bacterial resistance to the host immune system

Our aim is to identify bacterial factors involved in the passage through the intestinal epithelium of the host and characterize the strategies developed by bacteria belonging to the group B. cereus, to resist and adapt to the innate immune response during the early stages of infection.

Different aspects involved in the infectivity of B. cereus are examined:
i) Adhesion and cytotoxicity to eukaryotic epithelial cells.
ii) Interaction with phagocytic macrophage-like cells.
iii) Survival in macrophages.
iv) Resistance to the oxidative and nitrogen response.

Fundings: One health projet: Cross-sectoral framework for quality Assurance Resources for countries in the European Union – CARE 2020-2022, European Joint Project (EJP) One health. projet TOX-detect 2018-2020: Development and harmonisation of innovative methods for comprehensive analysis of foodborne toxigenic bacteria, ie. Staphylococci, Bacillus cereus and Clostridium perfringens. 2 M€; MEM-INRA MicrobNO Impact of the host nitrogen response following bacterial infection on the microbiota 2017-2018. 50 k€

.

Theme 2.- Diagnostic tools

PIMs’s diagnostic activity is focused on development of bioelectrochemical, PCR-based and paper-based  biosensors for applications in food and water security.  We develop sensing elements (DNA probes, aptamers, antibodies) that recognize bacterial biomarkers and innovative immobilization strategies for biomolecules, including chemical grafting, affinity interactions or formation of host-guest interactions.

Beside the elaboration of novel biosensors for bacterial detection, the PIMs team is highly experienced in discovery of new biomarkers of bacterial pathogenicity. PIMs present research interests include detections of B. cereus spp. in clinical and environmental samples and Campylobacter spp. in poultry meats. 

Fundings: Initiative d'excellence Paris Saclay. Idex. Projet Idex Bc 2017-2019: Biomarqueurs des Bacillus cereus pathogènes, 45 k€; INRA-prematuration 2017-2018: Biomarqueurs des Bacillus cereus pathogènes, 35 k€; Initiative d'excellence Paris Saclay. AAP Prématuration Idex. Projet BBC2 2018-2019: Développement d’un kit de détection de biomarqueurs des Bacillus cereus pathogènes, 65 k€; Poc in labs, Projet Idex OSCAR 2019-2020: OptimiSation et validation d’un kit de détection de CAmpylobacteR spp. dans la viande de poulet, 70 K€; H2020-MSCA-RISE 2020-2024, project IPANEMA: Integration of PAper-based Nucleic acid testing mEthods into Microfluidic devices for improved biosensing Applications, 2 M€.

Theme 3.- Therapeutic innovation: new antibiotic strategy

Antibiotics have drastically reduced the mortality associated with infectious diseases. However, their overuse prompted bacteria to develop resistance. Since 40 years, the rate of discovery of new antibiotics has constantly decreased and no “first in class” antibiotic has been proposed. Meanwhile, drug-resistant bacteria have spread, leading to 23000 deaths/year in the EU.

We identified an innovative therapeutic target for the development of new drugs. This target is a bacteria-specific protein with a key role in resistance to the host immune response. We identified inhibitors of this target able to specifically block bacterial survival during immune stress in vivo. These promising drug candidates are currently tested for safety to the host and for activity against serious threat pathogens.

Fundings: Initiative d'excellence Paris Saclay. AAP Prématuration Idex. Projet NewMed 2015-2016: Une nouvelle cible pour le développement d'antimicrobiens, 80 k€; SATT Paris Saclay. projet de maturation 2016-2018. An innovative target for the development of new drugs. 650 k€; Initiative d'excellence Paris Saclay. AAP Prématuration Idex. Projet NewMed2.0 2018-2019: Un antimicrobien innovant pour booster le système immunitaire, 70 k€; Toulouse White Biotechnology (TWB) Biosciences and bio production. Projet 2019-2020. PROFILING A MULTI-FUNCTION PROTEIN AS AN INNOVATIVE TARGET FOR THE DEVELOPMENT OF NEW DRUGS.

Theme 4.- Host/Pathogen/Microbiota

The innate immune response produces toxic substances to fight pathogens. However, these substances can also be deleterious for the host and its microbiota. Using Omic analysis and appropriate in vivo models, we study the impact of the innate immune response on the virulence of digestive pathogens and on the intestinal microbiota, and in return characterize the impact of the microbiota on the modulation of the host response and on bacterialpathogenicity. The study of this “ménage à trois” -host/pathogen/microbiota- may allow identifying new biomarkers for better diagnosis of infections and inflammatory diseases.

Fundings: MEM-INRA MicrobNO Impact of the host nitrogen response following bacterial infection on the microbiota 2017-2018, 55 k€; MEM-INRA. 2017-2018. Projet Metafoldscan. Structuring screening of microbial ecosystems, 50 k€

Theme 5.- Public communication

Last but not least, we set up a blog (https://bd-bacterie.com) and a multi-media comic to communicate with the general public on the use of antibiotics and on our current research.

Fundings: Fondation Carasso, COMPOSER LES SAVOIRS POUR MIEUX COMPRENDRE LES ENJEUX DU MONDE CONTEMPORAIN. Axe Art citoyen. Projet: Les antibiotiques ont la parole. 2016-2017, 50 k€; IDEX Paris-Saclay – Science et Société-La Diagonale Paris-Saclay2018: Bande dessinée multimédia, 5 k€; Ile de France 2018-2019. Projet: La Science pour tous, culture scientifique, technique et industrielle, 20 k€; IDEX Paris-Saclay – Science et Société-La Diagonale Paris-Saclay 2019-2020: Science et jeux, 5 k€