How do bacteria localize macromolecular complexes at their cell pole?

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Bacteria are unicellular organisms, as well as infectious agents, causative of multiple diseases. Since the 1950's, the threat of bacterial infections had largely subsided, due to the development of antibiotics. However, bacteria have showed an increasing amount of resistance to these in recent years. Indeed, we are fast-approaching a post-antibiotic world: an estimated 1.2 M people die annually from antibiotic-resistant bacterial infections world-wide, and projections indicate that this number will increase to ~ 10 M/year by 2050. We therefore urgently need to identify new approaches to combat bacterial infections. A previously-underappreciated aspect of bacteria is that they possess a very tightly-regulated internal organization, to ensure the proper localization of its various components and organelles, notably during cell division. In particular, a family of proteins (permed ParA/FlhG/MinD) is ubiquitous in bacteria, and has been shown to regulate the positioning of molecules and organelles at the pole of the cell. However, the mechanism of action of this family is currently not understood at the molecular level.Here, we propose to use a range of biophysical techniques to determine the general mechanism of action of this family of proteins. Specifically, we propose that the propensity of these proteins to form filaments, driving their cargo across the cell, is central to their function. We will notably exploit recent advances in cryo-electron microscopy, and in Artificial Intelligence-driven modelling, to understand how these proteins assemble at the atomic level, and how it allows them to recruit their respective cargo at the cell pole. This proposal will provide a fundamental shift in our understanding of bacterial cell biology, and could lead to the development of novel antibacterial therapeutics.