Understanding DivIVA mediated protein networks, central to the cell cycle in Gram-positive bacteria – Divinet

Bacterial cell division and elongation are fundamental processes for bacterial survival and proliferation. These processes required the coordination of a remarkable suite of protein interactions and biochemical reactions. This project will focus on DivIVA, a key cell division protein in two important bacterial families (Corynebacteriales and Streptococcaceae), whose morphogenesis processes differ from each other and from the classical gram-positive bacterial model B. subtilis. DivIVA proteins are characterized by a conserved membrane-binding domain, a coiled-coil domain, and variable intrinsically disordered regions. The latter can be phosphorylated, thus modulating the role of DivIVA in cell shape maintenance. Additional DivIVA paralogs have been described to play a crucial role in the bacterial cell cycle: GpsB (Streptococcaceae) and SepIVA (Corynebacteriales). Depletion of these proteins results in defects in bacterial growth and division. However, the precise molecular mechanisms underlying the roles of DivIVA-domain containing proteins in the bacterial cell cycle remain largely elusive. The central hypothesis of this project - supported by new insights obtained from phylogenetic analysis and high-confidence structural models - is that DivIVA proteins exhibit different assembly properties despite sharing similar molecular building blocks. These insights will guide protein design for structural and functional validation. Our goal is to shed light on the structural organization, functional diversity, and molecular mechanisms governing the localization and function of DivIVA proteins using two model organisms representative of Corynebacteriales (Corynebacterium glutamicum) and Streptococcaceae (Streptococcus pneumoniae) with industrial and biomedical potentials, respectively. By focusing on organisms with alternative growth modes, we seek to uncover unique and fundamental adaptations and mechanisms required to accommodate specific morphologies and growth modes.