The cross-regulation between two-component system BasS-BasR and ferric uptake regulator Fur in virulence gene expression in Edwardsiella piscicida

Edwardsiella piscicida is a widespread pathogen that infects a vast variety of fish species and causes hemorrhagic septicemia and significant property damage in the global aquaculture industry. E. piscicida employs type III and VI secretion systems (T3/T6SS) to penetrate and colonize macrophages, which are regulated by the EsrA-EsrB two-component system (TCS). In this study, we demonstrate that the BasS-BasR TCS positively regulates the expression of esrB and controls the secretion of T3/T6SS proteins. The regulatory protein BasR bound to the esrB promoter to activate the expression of virulence genes. Upon sensing the environmental ferric signals, BasS-BasR activated virulence gene expression through EsrB and simultaneously released Fur repression on esrB expression, eventually promoting E. piscicida colonization in turbot. Overall, this study revealed a new role of BasS-BasR TCS in virulence regulation and iron uptake, providing valuable insights into bacterial parthenogenesis. • BasR directly activates the expression of esrB. • BasS-BasR releases Fur repression on esrB expression. • BasS-BasR controls the secretion of T3/T6SS proteins. • BasS-BasR promotes E. piscicida colonization in turbot.