|The SAMe (Stress Adaptation and Metabolism) was created in 2018.
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.
ANR-FirstFeS: In search of the ancestral machineries for Iron-Sulfur biogenesis
Iron-sulfur (Fe-S) clusters are ancient and ubiquitous protein cofactors essential for life. It is thought that Fe-S clusters spontaneously assembled in the early Earth anaerobic environment rich in iron and sulfur. Rise of oxygen […]
Drug Discovery & Screening at Institut Pasteur
The Technological Targeted Action Drug Discovery and Screening (ATC-DDS) coordinates projects and collaborations at the Institut Pasteur Paris campus on therapeutic development. It raises awareness for DDS in basic research projects and stimulates intra-campus […]
Emerging Infectious Diseases
Ever since its very early days, the Institut Pasteur has been committed to tackling emerging infections, and its work has left an extraordinary legacy. Many emerging infectious diseases are zoonoses, in which an animal […]
Antimicrobial resistance is dramatically increasing worldwide and is becoming one of the most urgent public health threats. There is an urgent need for actions to reverse the curve of antimicrobial resistance dissemination and to […]
LabEx IBEID – Integrative Biology of Emerging Infectious Diseases
Presentation The aim of the Integrative Biology of Emerging Infectious Diseases (IBEID) project, coordinated by Professors Philippe Sansonetti and Pascale Cossart and currently coordinated by Carla Saleh and Philippe Bastin, is to develop a […]
2023Role of the Escherichia coli ubiquinone-synthesizing UbiUVT pathway in adaptation to changing respiratory conditions., mBio 2023 Jun; (): e0329822.
2023Bioenergetic State of Escherichia coli Controls Aminoglycoside Susceptibility., mBio 2023 Jan; (): e0330222.
2022An early origin of iron-sulfur cluster biosynthesis machineries before Earth oxygenation., Nat Ecol Evol 2022 Oct; 6(10): 1564-1572.
2022The Fe-S proteome of Escherichia coli: prediction, function and fate., Metallomics 2022 Mar; (): .
2022Cellular assays identify barriers impeding iron-sulfur enzyme activity in a non-native prokaryotic host., Elife 2022 Mar; 11(): .
2021Bacterial Approaches for Assembling Iron-Sulfur Proteins., mBio 2021 12; 12(6): e0242521.
2021Iron-sulfur biology invades tRNA modification: the case of U34 sulfuration., Nucleic Acids Res 2021 04; 49(7): 3997-4007.
2020Oxidative stress antagonizes fluoroquinolone drug sensitivity via the SoxR-SUF Fe-S cluster homeostatic axis., PLoS Genet 2020 Nov; 16(11): e1009198.
2020Making iron-sulfur cluster: structure, regulation and evolution of the bacterial ISC system., Adv Microb Physiol 2020 ; 76(): 1-39.
2019The SUF system: an ABC ATPase-dependent protein complex with a role in Fe–S cluster biogenesis, Research in Microbiology, 2019, pp.S0923-2508(19)30085-3. ⟨10.1016/j.resmic.2019.08.001⟩.
2018The ErpA/NfuA complex builds an oxidation-resistant Fe-S cluster delivery pathway, J. Biol. Chem. 2018 May;293(20):7689-7702.
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