There are at least ten times more bacteria in our body than human cells. Evolution has forced the emergence of several mechanisms, that are still unknown and that allowed the maintenance and the multiplication of these bacteria in the human microbiome (skin, respiratory, urinary and digestive tracts). These bacteria have co-evolved with humans and some mechanisms exist to discriminate commensal bacteria that are beneficial for the host health, versus pathogens that represent the world's leading causes of death particularly in the current era of global acquisition of antibiotic resistances.
Our research program aims at elucidating the mechanism of bacterial tolerance by studying the evolutionary events that led to the adaptation of symbiotic bacteria to human ecosystems. We recently demonstrated that some species evolved modifications of the essential bacterial component called peptidoglycan. This molecule is strongly recognized by the immune system. Several results point to the fact that these modifications could have played a role in the symbiotic bacterial adaptation by allowing immune-tolerance. We will study in details the host-bacteria communication processes and determine if some peptidoglycan motifs could participate in this cross-talk. We will also try to determine if evolved modifications of the peptidoglycan from pathogens could participate in the defence against neighbour bacterial competitors.
These competitors that are found in the human microbiome, such as the nasopharynx, can secrete peptidoglycan-targeting effectors that kill the pathogen. Finally, Mycobacterium tuberculosis evolved a specific way of regulating the synthesis of its cell wall. We will study how this evolution could have helped this bacterium to become one of the major human threats.
All together, results from this research program will not only serve in the design of new and innovative therapeutic strategy aiming at fighting bacterial pathogens but will also serve in the development of anti-inflammatory molecules based on specific PG motifs.