Two-Component Systems in Pasteurellaceae and Their Roles in Virulence.

Two-component systems (TCSs) are widespread in bacteria and archaea, with only limited presence in eukaryotes. These signaling mechanisms detect environmental changes and adjust gene expression to survive and adapt. In this review, TCSs were examined within the Pasteurellaceae family, focusing on how closely related organisms employ similar systems to regulate infections and stress responses. Comparative analysis revealed that homologous TCSs can differ markedly in the signals they detect and in the genes or virulence factors they control, underscoring the functional diversity that has evolved even within this family. Inconsistencies in nomenclature across studies are also identified, which complicate data integration and cross-species comparisons. Given these challenges, the need for unified naming conventions and broader, system-level analyses is highlighted. It is further proposed that emerging computational tools-including molecular modeling, molecular dynamics, and neural network-based analyses-offer powerful strategies to predict signaling interactions, identify conserved regulatory models, and clarify how these systems contribute to bacterial adaptation and pathogenicity.