One of the most fundamental challenges of bacterial cell metabolism is to ensure a reliable balance of carbon, electrons and energy in the highly variable biological environment. In this context, bacterial respiration is essential as it provides energy in the form of ATP and of an electrochemical gradient generated across the membrane which powers transport of molecules (proteins, ions and antibiotics) or cell motility.
Our focus on anaerobic bacterial respiration is stimulated by its emerging role in human microbiota and its impact on health. Indeed, inflammation of the gastrointestinal and respiratory tracts is associated with the bloom of facultative anaerobic γ-proteobacteria. Most respiratory complexes using alternative substrates to O2 are molybdoenzymes belonging to an ancient protein family found in most prokaryotes.
Using multi-scale approaches ranging from atomistic investigation of molecular processes to cell biology studies, our team studies (i) how to get a fully active respiratory complex in the cell, (ii) what determines reactivity of respiratory complexes toward their substrates and (iii) how optimization of respiration is made in response to fluctuating environmental conditions. To this end, collaborations are settled with laboratories working in various fields such as chemistry, physics, crystallography, genetics, microscopy and medicine as interdisciplinarity is key to investigate complex biological systems.
In the recent years, we have :
- identified and provided a comprehensive understanding of a new dedicated chaperone involved in the activation of formate dehydrogenases (Thome 2012 JBC, Arnoux 2015 Nat com)(Figure 1),
- provided unprecedented structural details about the mode of interaction of quinones with respiratory complexes (Arias-Cartin 2010 JACS, Grimaldi 2012 JBC, Rendon 2015 BBA),
- unveiled a new function of lipid binding to respiratory complexes (Arias-Cartin 2011 PNAS),
- demonstrated that dynamic subcellular localization of respiratory complexes is a critical factor in the control of bacterial respiration (Alberge 2015 eLife)(Figure 2).
Figure 1 : How to get a fully active respiratory complex in the cell ? Production of active formate dehydrogenases relies on the activity of a dedicated chaperone ensuring sulfur atom transfer from IscS to the molybdenum cofactor prior its subsequent delivery to the enzyme.
Figure 2 : How optimization of respiration is made in response to fluctuating environmental conditions ? Nitrate reductase is a major respiratory complex under anaerobiosis in most γ-proteobacteria including Escherichia coli. We showed that its localization is submitted to tight spatiotemporal regulation in response to metabolic conditions.
- Prof Bruno Guigliarelli (BIP, Marseille, France)
- Dr Christophe Léger (BIP, Marseille, France)
- Dr Barbara Schoepp-Cothenet (BIP, Marseille, France)
- Dr David Pignol (LBC, Cadarache, France)
- Dr Dominique Schneider (TIMC-IMAG, Grenoble, France)
- Dr Didier Marguet (CIML, Marseille, France)
- Dr Olivier Neyrolles (IPBS, Toulouse, France)
- Prof Céline Brochier-Armanet (LBBE, Villeurbanne, France)
- Prof Eric Oswald (IRSD, Toulouse, France)
- Dr Dieter Jahn (TU Braunschweig, Germany)
- Prof Ralf R. Mendel (TU Braunschweig, Germany)
- Prof Thorsten Friedrich (Freiburg University, Germany)
Job opportunities :
We are always interested in recruiting exceptional postdoctoral or PhD candidates interested in bacterial cell metabolism. Applicants should contact Axel for any project by e-mail.