LAUSR

&NA; Aeromonas hydrophila is a causative pathogen of many infectious diseases in fish and human. The two‐component regulatory system enables bacteria to respond to a wide range of stimuli, growth conditions and environments. The two‐component system CpxA/R is prevalent in microorganisms and involved in the pathogenesis of a number of pathogens. In this study, we generated a &Dgr;cpxA/R mutant of A. hydrophila ZYAH72 to explore the biological functions mediated by the CpxA/R in this organism. Compared with the wild type strain, the knockout mutant strain &Dgr;cpxA/R exhibited a significant impairment in adherence to human epithelial cells Caco‐2 and resistance against host killing in fish blood. However, the mutant strain and the wild type strain showed no difference in the cytotoxicity assay, which revealed that the absence of CpxA/R did not influence the cytopathic effect of this pathogen in vitro. Furthermore, the virulence of &Dgr;cpxA/R was attenuated in zebrafish (Danio rerio) and grass carp (Ctenopharyngodon idella) infections, with reduced mortality or delayed death time. These findings suggest that CpxA/R is required for the virulence of A. hydrophila.