3rd international Biometals webinars
Authors: Michaud-Soret Isabelle , Maret Wolfgang , SCHALK Isabelle 
Published: March 2024

Introduction to the 3rd Biometals webinars and tribute to Pierre Cornelis

Welcome to the 3rd international webinars series. For those who don't already know, these webinars have been set up by the international Biometals society and the journal Biometals with the help of Cassyni platform.

* The aim is to promote research in the field of metal interactions in biology and to encourage the interdisciplinary exchange of information at international level.

Today we welcome two speakers:

* Wolfgang Maret will be talking about zinc homeostasis, zinc containing zinc signaling and zinc in relation with human diseases. Zinc is a metallic element whose role has been underestimated for far too long...so affine and yet so discreet! So affine if we consider the irwing Williams series, but quite silent metal ions in term of spectroscopy (except using Xray absorption). X-ray structures reveal zinc in so many proteins, and mass spectrometry reveals it in so many biological environment.

* The 2nd speaker, Isabelle Schalk was invited to pay tribute to Pierre Cornelis, who left us too early last december.
Pierre was president of the international biometals society and associate editor due Biometals. We will miss him. As Pierre, Isabelle work focus on iron homeostasis in Pseudomonas.Iron is essential but may be scarce in some medium conditions such as infected host or environment. So, microorganisms develop tricks to be sure to get their required micromolar internal concentration. Isabelle will show some Pseudomonas tricks that involve iron uptake in complex with several siderophores

Controlling 3000 human cellular zinc proteins and intra- and extracellular Zn2+ signalling

In 1869, Jules Raulin, a student of Louis Pasteur working in Lyon (France), reported that zinc is essential for the mold Aspergillus niger. It took another 100 years until the late Ananda Prasad and his colleagues showed that zinc is an essential micronutrient for humans. In the last 80 years, roles of zinc as catalytic metal ion in an increasing number of enzymes and as a structural metal ion in proteins such as zinc fingers involved in protein-DNA, protein-RNA, and protein-protein interactions were revealed, culminating in bioinformatics investigations that estimated that at least 3000 human proteins are zinc proteins. In the last decades, additional modes of action emerged, namely that Zn2+ ions have a regulatory role akin to and complementary to Ca2+ ions in intracellular signalling and are secreted from vesicular stores as extracellular autocrine, paracrine, and possibly endocrine messengers. These signalling functions include additional targets that further increase the number of zinc-dependent proteins. The control of all these zinc-dependent processes requires a complex system of regulation. Minimally, it involves 24 zinc transporter proteins that increase or decrease cytosolic zinc concentrations, a dozen metallothioneins as dynamic metal buffers to modulate the availability of zinc at remarkably low concentrations, transcription factors serving as metal sensors, and a recently discovered metallochaperone for zinc. After focusing on the coordination dynamics of zinc in the chemical and biochemical mechanisms employed in this complex zinc homeostatic system and the important relationship between zinc metabolism and redox metabolism, I will briefly introduce our present work on some aspects of zinc in human disease (diabetes and inflammatory conditions of the skin, gut, and connective tissue).

Pseudomonas aeruginosa and Its Proficiency in Utilizing Numerous Siderophores Produced by Other Microorganisms

Pseudomonas aeruginosa, a ubiquitous bacterium found in diverse natural and man-made environments, serves as a pathogen for plants, animals, and humans. Like most living organisms, iron is indispensable for its growth. The bacterium has developed intricate systems, relying on the use of siderophores, to access iron and maintain homeostasis, crucial for survival in dynamic host environments. P. aeruginosa can produce two siderophores and utilize various siderophores from other bacteria. These iron uptake pathways predominantly rely on TonB-dependent transporters (TBDTs) for iron uptake across the outer membrane. Through proteomic and qRT-PCR analyses, we explored how P. aeruginosa modulates its iron import pathways in response to environmental cues. Additionally, fluorescent reporters fused with TBDT promoter regions enabled us to monitor TBDT expression under different growth conditions. Mathematical modeling revealed distinct transcription and expression profiles for various TBDTs. Our findings offer precise insights into how P. aeruginosa adjusts the expression of its iron-uptake pathways, demonstrating phenotypic plasticity mechanisms in response to varying iron levels and competition pressures.