The PIMs team is expert in the study of bacterial resistance to the host immune system. We characterize the effects of the immune response on pathogenic bacteria and develop new strategies of anti-virulence to combat bacterial infections.
Our team develops innovative strategies to combat bacterial infections based on our knowledge and expertise on bacterial resistance to the host immune response. We mainly focus on bacteria from the ESKAPE group (ie, S. aureus, K. pneumoniae, P. aeruginosa, E. coli…) for which the WHO has pointed an alarming antibiotic resistance issue.
We also aim to characterize the impact of the host immune response on the gut microbiome and on the development of pathogen’s virulence. The projects of the team are divided into four main axes:
The aim of the team is to develop an ambitious project at the interface between fundamental and applied science to tackle the increasing threat of antibioresistance. We identify factors involved in bacterial virulence and characterize the strategies developed by pathogenic bacteria to resist and adapt to the innate immune response during the early stages of infections.
Different aspects involved in the infectivity are examined:
Antibiotics have drastically reduced the mortality associated with infectious diseases. However, their overuse has prompted bacteria to develop resistance. Since 50 years, the rate of discovery of new antibiotics has constantly decreased and no “first in class” antibiotics have been proposed. Meanwhile, drug resistance bacteria are becoming more and more present leading to 23 000 deaths every year in the EU.
We identified an innovative therapeutic target for the development of new drugs. In our study for virulence factors, we identified the Mfd protein as one of them. First identified in B. cereus, we showed that this protein is bacteria specific, has a key role in resistance to the host immune response and is found in every bacteria. Following this discovery, we identified inhibitors of this target able to specifically block bacterial survival during immune stress in vivo. These promising anti virulence drugs are currently being tested for the safety to the host, for resistance induction and for their activity against bacteria from the ESKAPE group in vitro and in vivo. This work is done in close collaboration with CEA, Galien Institut and MaIAGE unit (INRAE).
On the other hand we also focus on the study of the bacterial target Mfd to better understand its various functions in DNA repair, transcription, evolvability and virulence.
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 vitro and in vivo models, we study the impact of the innate immune response on the virulence of bacterial pathogens and on the intestinal microbiota, and in return characterize the impact of the microbiota on the modulation of the host response and on bacterial pathogenicity. The study of this “ménage à trois” -host/pathogen/microbiota- may allow identifying new biomarkers for better diagnosis of infections and inflammatory diseases.
Last but not least, we set up a blog with a comic to communicate with the general public on the use of antibiotics. We also developed a board game on antibio-resistance that can be purchased online.
All the team publications are available in the PIMS-MICALIS HAL collection.
