The calcium signal regulatory network and the roles of calcium-binding proteins in bacteria

Calcium ions are ubiquitous second messengers in bacteria that play a pivotal role in their environmental adaptation, pathogenicity, and the regulation of core life activities. Despite lacking the sophisticated calcium buffering pools associated with the endomembrane system in eukaryotic cells, bacteria have evolved a unique and elaborate mechanism to maintain intracellular calcium homeostasis and decode calcium signals. This article innovatively reviews the regulatory networks of calcium signaling and the roles of calcium-binding proteins in bacteria. Various families of bacterial calcium-binding proteins (including proteins with EF hand domains, the βγ-crystallin superfamily, RTX proteins, and bacterial immunoglobulin-like (Big) domains) are comprehensively described. These calcium-binding proteins exhibit remarkable pleiotropic properties by undergoing conformational changes induced by calcium ions (such as transitions from an unordered state to an ordered state or the formation of specific structures), integrating multiple functions (such as calcium buffering, signal sensing, and functional regulation). In addition, the role of calcium signals and calcium-binding proteins in regulating various biological processes such as bacterial movement, biofilm formation, cell differentiation, and pathogenicity has been summarized. This work provides an important theoretical basis and potential targets for the development of novel anti-biofilm strategies targeting calcium signaling pathways.