Fish-derived soluble cues remodel the transcriptome of Aeromonas salmonicida in marine environments

Aeromonas salmonicida is an important pathogen of freshwater and marine fish, yet little is known about its transcriptional responses to seawater and soluble cues released by susceptible marine hosts. We investigated the response of a highly virulent A. salmonicida strain to seawater and fish-derived cues using dialysis bags that physically separated bacteria from lumpfish (Cyclopterus lumpus) while allowing exposure to soluble host-derived compounds. Immersion challenge with 10⁶ CFU/mL of A. salmonicida for 40 min resulted in 100% lumpfish mortality within 14 days, confirming susceptibility to waterborne infection. Transcriptomic analysis of A. salmonicida identified 1,389 and 1,184 differentially expressed genes after 40 min exposure to seawater (SW) and seawater in the presence of lumpfish (SWF), respectively, relative to culture conditions. Seawater induced extensive remodeling of stress and redox homeostasis, transport, surface and sensory systems, iron homeostasis, and transcriptional regulation, with reduced expression of cell-division and cell-envelope biosynthetic functions. Direct comparison of SWF with SW identified 442 bacterial DEGs, including 225 with higher and 217 with lower expression in SWF. Fish-derived cues were particularly associated with increased expression of amino-acid and central carbon metabolism and nutrient and osmolyte transport. The pASAL5-encoded type III secretion system showed an induction-dominated response to seawater and component-specific modulation by fish-derived cues. These findings demonstrate that seawater initiates transcriptional remodeling of environmental and virulence-associated functions before direct host contact, while host-derived cues further modify metabolic, transport, and T3SS-associated responses.