Responsable : Olivier Espéli

Recherche : Cell cycle and chromosome dynamics

1Bacteria are highly organized cells that can multiply rapidly when the environment is favorable. To reach a fast growth rate bacteria rely on a strongly regulated cell cycle that coordinate the genome replication, chromosome segregation, cell elongation and division. However when the environment is less favorable the bacteria adapts their growing regime to protect themselves. The lack of nutrients or the presence of stress (reactive oxygen species, acid pH, genotoxic compound, etc.) induce gene expression response that will helps to cope with the stress. The fact that these stress response also involve modulation of the cell cycle is an emerging topics. Most of the work performed in my group concerns cell cycle regulation and its adaptation to changing environment.

2The first axis of research concerns the regulation of chromosome segregation and organization (Lagomarsino et al., 2015). We recently demonstrated that chromosome segregation is under the control of a topoisomerase (TopoIV) which highly regulated activity is the key element to initiate chromosome segregation (El Sayyed et al., 2016 ; Lesterlin et al., 2012). Interestingly in the presence of genotoxic drugs that create double strand breaks on the replicative chromosome this segregation program is perturbed and sister chromatids become attached by a cohesin like protein induced by the SOS regulon (Vickridge et al., Nature Communications, in press). The control of chromosome segregation in response to genotoxic stress is a process important for DNA repair and appear to be conserved in other bacteria such as the radioresistant bacterium Deionococcus radiodurans (Passot et al., 2015). From these work also emerged the intriguing observation that chromosome conformation might be profoundly changed by the presence of environmental stress. We have developed a collaborative project with the group of Roman Koszul in the Institut Pasteur to survey chromosome conformation in different conditions and decipher the respective roles the stress response itself and the change in the gene expression program on chromosome conformation.

3The second axis of our research concerns the cell cycle adaptation to environment that bacteria might encounter when they colonize a host. We have focused our interest on a particular type of E. coli that has been found in the gut of Crohn disease’s patients. This E. coli strains, called AIEC, can invade epithelium and colonize macrophages. Inside macrophages they are growing in a highly stressing environment. We recently demonstrated that in the macrophage AIEC bacteria cope with the stress by a profound adaptation of their cell cycle. A large part of the population halt their cell cycle and enter in a dormant like stage that help them to resist to the stress and also to antibiotic treatments. Some AIEC bacteria nevertheless are able to growth inside the macrophage and this might correspond to their ability to find nutrients in their immediate environment. Our efforts are dedicated to the understanding of the mechanisms involved in these cell cycle adaptations and the interplay between the bacteria and its host.

Publications

4El Sayyed H., Le Chat L., Lebailly E., Vickridge E., Pages C., Cornet F., Cosentino Lagomarsino M. et Espéli O., « Mapping topoisomerase IV binding and activity sites on the E. coli genome », PLoS genetics, vol. 12, n^o 5, 2016, e1006025, DOI : 10.1371/journal.pgen.1006025.

Lagomarsino M.C., Espéli O. et Junier I., « From structure to function of bacterial chromosomes: Evolutionary perspectives and ideas for new experiments », FEBS letters, vol. 589, n^o 20 Pt A, 2015, p. 2996-3004, DOI : 10.1016/j.febslet.2015.07.002.

Passot F.M., Nguyen H.H., Dard-Dascot C., Thermes C., Servant P., Espéli O. et Sommer S., « Nucleoid organization in the radioresistant bacterium Deinococcus radiodurans », Molecular Microbiology, vol. 97, n^o 4, 2015, p. 759-774, DOI : 10.1111/mmi.13064.