Multi-Omics Study on the Molecular Mechanisms of Tetraodon Nigroviridis Resistance to Exogenous Vibrio Parahaemolyticus Infection

Abstract

Vibrio parahaemolyticus is an important marine pathogen that causes inflammation and even death in teleost fishes. It has brought significant economic losses to the aquaculture industry as well as high risks to the sustainable development of marine fisheries. In the present study, the fish Tetraodon nigroviridis and the bacterial pathogen Vibrio parahaemolyticus were used to explore the molecular mechanisms underlying the immune response of T. nigroviridis to V. parahaemolyticus exogenous infection. The microRNA (miRNA)–mRNA–protein omics and corresponding experimental validation, followed by comparative analysis, revealed several differentially expressed genes involved in various components of the immune system, including the following: complement system, chemokines, lysosomes, phagocytes, B-cell receptor signaling pathway, T-cell receptor signaling pathway, Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway, and phospholipid metabolism, among others. Especially, the complements component 3 (C3) gene and protein expression levels were significantly higher after V. parahaemolyticus infection, and miRNAs targeting C3, including mir-6089-y, mir-460-y, and mir-1584-x, were significantly down-regulated. The gene and protein expression levels of complement 1 subunit qA (C1qA) were significantly down-regulated, while mir-203 targeting C1qA was significantly up-regulated. Overall, four complement genes (C1qA, IG, C3, and C5), which are key genes in the classical pathway of complement system activation for inflammatory response, were identified. Evolutionary analysis suggested that T. nigroviridis, acquired an increased ability to recognize pathogens by evolving a more complex complement system than terrestrial vertebrates. In addition, quantitative real-time polymerase chain reaction showed high consistency with the obtained multi-omics results, indicating the reliability of the sequencing data generated in the present study. In summary, our findings can serve as a fundamental basis for further in-depth multi-omics studies on the inflammatory processes of aquatic pathogens hindering fish sustainable production.