Microbiology DPT seminar :
Tripartite interactions between the host, the bacterium and the bacteriophage (The Good, the Bad and the Ugly ?)
by Laurent DEBARBIEUX
group : Interactions Bacteriophages Bacteria in Animals
Unit : Molecular Biology of Gene in Extremophiles – Microbiology DPT
Abstract : Bacteriophages shape and structure bacterial communities in all natural environments, from oceans to soil, as well as in the microbiota associated with the human body. Interactions between these antagonistic populations have been studied extensively in vitro, but much less is known about their relationship with mammalian bodies.
We are using several animal models to decipher the mechanisms underlying tripartite interactions between host cells, bacteria and bacteriophages. More specifically, we found that in the gastro-intestinal tract (GIT) of mice virulent bacteriophages display uneven degrees of success in reducing the density of their bacterial target (Escherichia coli). We identified several factors influencing the efficacy of bacteriophages in the GIT including downregulation of specific bacterial genes, spatial refuges and, unexpectedly, pathogenicity islands. We also observed that bacteriophages evolve by jumping from one bacterium to another to persist in the GIT. In addition, we uncovered an original homologous intragenomic recombination event showing that bacteriophages use their own genome to evolve and develop new properties.
Many genes in bacteriophage genomes code for proteins of unknown functions. Some are expected to impact negatively bacteria. We identified such a protein that is affecting bacterial morphology. Interestingly, we discovered that this protein interacts with bacterial membrane stress response proteins and leads to increase susceptibility of bacteria to b-lactams. The virulent bacteriophage expressing this protein was selected for its efficacy to treat bacterial infection in a murine model of acute pneumonia induced by Pseudomonas aeruginosa. Our efforts to characterize therapeutic bacteriophages is driven by the renew interest on phage therapy as a weapon against antibiotic-resistant bacteria. We recently demonstrated that the success of phage therapy relies on the synergistic action of bacteriophage with the immune system, highlighting the necessity to go beyond the simplistic ability of bacteriophages to form plaques on Petri dishes.
I will discuss that depending on the point of view, the Good, the Bad and the Ugly will not necessarily be the Host, the Bacterium and the Bacteriophage.
Building: Centre François Jacob
Address: 25-28 Rue du Dr Roux, 75015 Paris, France