A total infectome framework for resolving complex disease etiology in aquaculture

Area of Science:

• Aquatic animal health
• Microbiology
• Disease diagnostics

Background:

• Traditional pathogen isolation struggles with complex infections.
• Metatranscriptomics captures the total infectome but lacks etiological specificity.
• Overwintering syndrome (OWS) in grass carp is a significant unresolved aquaculture disease.

Purpose of the Study:

• To develop an integrated strategy for identifying the primary etiological agent in complex aquaculture diseases.
• To resolve the causative agent of overwintering syndrome (OWS) in grass carp.
• To establish a generalizable framework for pathogen discovery and causal inference.

Main Methods:

• Integrated strategy linking comparative total infectome analysis with targeted isolation, experimental infection, and validation.
• Multi-organ metatranscriptomic profiling of healthy and diseased grass carp.
• Experimental infection with prioritized candidate pathogens and post-challenge infectome validation.

Main Results:

• Identified 107 microorganisms across viruses, bacteria, and eukaryotes in grass carp.
• Prioritized Flavobacterium psychrophilum as the primary etiological agent based on disease enrichment, abundance, and dissemination.
• F. psychrophilum infection alone reproduced OWS clinical signs, pathology, and mortality; warming promoted disease progression.

Conclusions:

• Flavobacterium psychrophilum is the primary causative agent of overwintering syndrome in grass carp.
• The integrated infectomics approach successfully resolved a complex aquaculture disease.
• The developed framework is generalizable for identifying causal agents in complex infectious diseases.