Stress Adaptation and Metabolism (SAMe)

Because it is the hallmark of bacterial life, analysis of bacterial stress adaptation has been at the center of our interest since more than two decades and will feed projects in the next years. Most bacteria multiply in changing environments and need to adapt to fluctuating concentration in nutriments, chemicals, toxic or not, or must keep up with physical challenges. Thus, one can describe bacterial stress adaptation as a 3-step process: (i) sensing of the stress causing perturbation, (ii) modification of cellular processes to protect, repair or mitigate unwanted effects and (iii) stabilization of a new cellular state (homeostasis) in the conditions that caused unbalance in the first place.

Out interests aim at deciphering mechanistic basis of biological processes ubiquitous and conserved in living organisms, for which E. coli can hold as a model. [Fe-S]-based biology stands as a perfect example of such processes. Since very early stages of evolution, their remarkable chemical versatility has been exploited by many biological processes, pathways and mechanisms and this is without surprise that [Fe-S] based biology motors several “stress sensing and adaptation” circuits. Our past, present and future projects aim at appreciating the contribution of [Fe-S] to cellular homeostasis.

Stress-inducing events that we are studying are redox changes, such as aerobiosis vs anaerobiosis, presence of toxic compounds, such as NO or antibiotics, and nutrient limitation, such as iron scarcity, fatty acids or sulfur limitation. Cellular modifications that contribute to a new stable state under study include genomic evolution, genetic reprogramming, tRNA modification, bioenergetics versatility and fatty acid/lipid metabolism. We will capitalize on our phylogenomic studies to raise new questions about the evolution of [Fe-S] biogenesis systems in procaryotes. The contribution of [Fe-S] proteins to sense and convey sulfur limitation, as suggested by our recent study, or NO signals will bring us to an integrated view of the cell wherein protein translation talks with sulfur homeostasis, and nitrosylation might be connected to carbon degradation. We found versatility of respiratory chains to be a key factor in susceptibility to aminoglycoside. Its exploitation for adapting to different compartments in the gut will next lead us to decipher the role of a AAA ATPase at the crossroad between membrane biology and bioenergetics.

Most projects are using E. coli lab strain as a model, yet in some cases pathogenic (Shigella, UTI) or natural E. coli isolates will be studied such as to position our findings within the context of bacterial pathogenesis and/or microbiota dynamics. The development of these projects will rest on our expertise in molecular microbiology, biochemistry and genetics, our collaboration with experts in complimentary fields (chemistry, phylogenomicists, physicists, cell biologist, “microbiote microbiologists”) and the availability of cutting-edge platforms (omics, biophysics, structural biology) present at the Institut Pasteur.