QseBC regulates in vitro and in vivo virulence of Aeromonas hydrophila in response to norepinephrine.

The inter-kingdom communication between host and pathogenic bacteria mediated by the host hormones epinephrine (Epi)/norepinephrine (NE)/autoinducer-3 (AI-3) and transduced by the bacterial two-component signal transduction system QseBC has been well demonstrated in mammalian pathogens. Aeromonas hydrophila, a common opportunistic pathogen in freshwater aquaculture, responds to NE by increased bacterial growth and enhanced virulence. However, the underlying mechanisms remain poorly understood. Our study demonstrated that deletion of qseB and qseC significantly inhibited NE-promoted growth, biofilm formation, and hemolytic activity of A. hydrophila. The adhesion ability of ΔqseB and ΔqseC to J774a.1 cells was significantly decreased compared with the wild-type strain in the presence and absence of NE, whereas NE still enhanced the adhesion ability of the mutant and wild-type strains with a similar effect, suggesting that NE-enhanced cell adhesion was independent of QseBC. Moreover, QseBC did not affect the swimming and swarming motility of A. hydrophila with or without NE. Quantitative real-time PCR analyses revealed the down-regulated expression of some virulence-related genes (hly, ast, act, aerA) in each mutant compared with the wild-type strain in the presence of NE. Tilapia infection experiments indicated that deletion of qseB or qseC weakened NE-promoted virulence of A. hydrophila. In conclusion, our study suggests that NE stimulates the growth, biofilm formation, and hemolytic activity of A. hydrophila and enhances the virulence of the pathogen in fish via the QseBC system.