Keynote #2 | Marianne Ilbert
Prof. Marianne Ilbert is a researcher at the NRS Laboratory of bioenergetic and protein engineering, France.
As a microbiologist and biochemist specializing in molecular chaperones and metalloproteins, her current project focuses on deciphering the impact of copper excess on bacteria. Their recent findings indicate that even a slight excess of copper in a cell can lead to the inactivation or aggregation of numerous proteins, significantly disrupting proteostasis. In such scenarios, chaperone proteins emerge as crucial defence mechanisms.
This work enhances our understanding of copper's mechanisms of action and paves the way for its optimization in biomedical and biotechnological applications, copper being a powerful antimicrobial agent.
Prof. Marianne Ilbert on ORCID...
Copper, a friend or a foe?
Ludovic Dubard, Glaucia Pinheiro, Nora Lahrach, Lisa Zuily, Marie-Thérèse Giudici-Orticoni, Véronique Receveur-Brechot, Pierre Genevaux, Olivier Genest, Olivier Sénèque, Peter Faller and Marianne Ilbert
Unité de Bioénergétique et Ingénierie des Protéines, Institut de Microbiologie de la Méditerranée, CNRS-UMR7281, Aix-Marseille Université, 13009 Marseille, France
Copper's paradoxical role as both an essential nutrient and a toxic element presents a unique opportunity for biomedical applications. Our latest research reveals that a slight intracellular copper excess can disrupt bacterial proteostasis independently of reactive oxygen species (1), thereby challenging the traditional understanding of copper's toxicity. In agreement with these results, we have demonstrated the role of molecular chaperones as defense mechanisms against copper stress in bacteria. Notably, we have identified a novel regulatory mechanism in zinc-binding molecular chaperones (2), wherein copper excess triggers chaperone activation to counteract protein aggregation. This occurs through transmetallation-based regulation. Our ongoing research focuses on the potential of copper-ligand complexes (Cu-L) as highly efficient antimicrobials (3) and on understanding their mechanisms of action. This research is crucial for deciphering copper's dual role in biology and has significant implications for the development of new antibiotics, addressing soil contamination, and exploring links to neurodegenerative disease
References
(1) Zuily L., Lahrach N., Fassler P., Sénèque O., Denis Y., Faller P., Genest O., Genevaux P., Castanié-Cornet M.P., Jakob U., Reichmann D., Giudici-Orticoni MT, Ilbert M. Copper Induces Protein Aggregation, a Toxic Process Compensated by Molecular Chaperones, 2022, Mbio, 2022 Apr 26;13(2):e0325121, doi: 10.1128/mbio.03251-21.
(2) Fassler R., Zuily L., Lahrach N., Ilbert M*., Reichmann D*. The central role of redox-regulated switch in bacteria. Front Mol Biosci. 2021 Jul 2;8:706039. doi: 10.3389/fmolb.2021.706039. eCollection 2021.
(3) Zuily L., Lahrach N., Falcone E., Bouraguba M.., Lebrun V., Lojou E., Giudici-Orticoni M.T., Faller P*., Ilbert M*. (2023) Toxicity of Cu on Bacteria: from boosting to silencing. Book Chapter in World Scientific Publishing Company. Copper Bioinorganic Chemistry. p1-44 doi: 10.1142/9789811269493_0001