Looking at bacterial cell poles from a liquid-liquid phase separation of intrinsically disordered proteins perspective

Bacterial cell poles play a fundamental role in several cellular processes, such as cell cycle, chemotaxis, cell differentiation, development, growth, and structure of the bacterial cell, as well as protein localization. Using a set of bioinformatics tools, we evaluated the probability of 19 bacterial cell pole-related proteins to be disordered and undergo spontaneous liquid-liquid phase separation (LLPS). Our analysis revealed that11 cell pole-related proteins are predicted to be highly disordered, 7 proteins are moderately disordered, and only one protein is expected to be highly ordered. Furthermore, this intrinsic disorder propensity is mostly evolutionary conserved. Most of the analyzed 19 cell pole-related proteins were found to be associated with the LLPS process, with TipN, PopZ, and PBP2A being capable of spontaneous phase separation, RacA, Noc, PBP1A/1B, ParB, PBP3, PBP2B, FtsZ, MipZ, MinD, and MreB being expected to potentially serve as droplet clients, and with the remaining proteins (DivIVA, ComN, Maf, PBP4, MinC, and MinJ) being predicted to be unrelated to LLPS. The results suggested that FtsZ, DivIVA, and MiPZ serve as the main regulatory proteins, being well-known for their role in forming the septum and chromosomal segregation. Furthermore, PopZ and TipN proteins contribute to high stress resistance. Clarifying the function and effects of each mechanism gives insight into the organization of bacterial cells and some strategies for antimicrobial targets.