The MAPVAP project (pre-clinical mechanistic assessment of two bacteriophage cocktails targeting multidrug-resistant Pseudomonas aeruginosa and Escherichia coli for the treatment of ventilator-associated pneumonia) is a collborative research program financed by France and Germany through the 2019 dedicated call on antimicrobial resistance.
Ventilator-associated pneumonia (VAP) causes high morbidity and mortality and is a major health care cost driver. VAP is frequently caused by multidrug resistant (MDR) bacteria with Pseudomonas aeruginosa and Enterobacteriaceae being the most relevant pathogens and listed as critical on the WHO’s priority pathogen list. Bacteriophage therapy provides an attractive solution to the increasing failure of antibiotics, but scientific and translational data addressing the emergence of bacteriophage resistance, the control of biofilm forming bacteria, detailed immuno-safety and immune-efficacy are largely missing. Using two established bacteriophage cocktails specific for P. aeruginosa or Escherichia coli that originate from German and French teams, respectively, we will join forces to (1) characterize bacteriophage-resistance development during in vivo pre-clinical treatment, (2) decipher the impact of these cocktails on the respiratory and intestinal microbiota as well as on microbiota-dependent immune responses, (3) evaluate the efficacy of the cocktails to penetrate biofilms produced in vitro and ex vivo on explanted human lung tissue, (4) investigate the direct interaction of phages with the immune system and the mechanistic basis for the synergy between innate immune cells and bacteriophages during therapies, and (5) characterize by mathematical modeling the efficacy of these cocktails in vivo and propose optimized treatment regimens.
In MAPVAP, we will synergistically combine our extensive and complementary expertise and resources to strengthen phage therapy in France and Germany and significantly improve its transition towards human treatments.
2020-09-25: TC meeting (update on the website and data managment)
2020-07-17: TC meeting to resume activities after Covid-19 lockdown
2020-02-27: Kick-off meeting (La Charité, Berlin)