Integrated analysis of transcriptomics and metabolomics reveals the role of hypoxia inducible factor HIF-1α in the regulation of pathogenic Vibrio infection in shrimp

Vibriosis is one of the most prevalent and severe bacterial diseases in shrimp aquaculture. Shrimp gills are important for respiration, making them vulnerable to hypoxia, and they also serve as entry sites for pathogenic bacteria. Hypoxia-inducible factor-1 (HIF-1) is a central transcription factor in cellular oxygen sensing and regulation, however, its function in Vibrio infection remains unclear. In this study, a new gill-specific expressed HIF-1α ( LvHIFn-1α ) was identified in the Pacific white shrimp Litopenaeus vannamei . To investigate the roles of HIF-1α in Vibrio infection, LvHIFn-1α was knocked down by RNA interference (RNAi) and comparative transcriptome and metabolome analyses were conducted on gills of the LvHIFn-1α -interfered shrimp and control shrimp at 0 and 6 h after immersion infection with V. parahaemolyticus . Integrated analysis showed that knockdown of LvHIFn-1α led to remarkable dysregulation of several pathways at both transcriptional and metabolic levels, including glycolysis/gluconeogenesis, glutathione metabolism, nicotinate and nicotinamide metabolism and arachidonic acid metabolism. Most immune-related genes, such as C-type lectins, anti-lipopolysaccharide factors (ALFs) and prophenoloxidase (proPO) system-related genes, were highly expressed in the dsHIFn-1α group. After V. parahaemolyticus infection, LvHIFn-1α knockdown further exacerbated alterations in redox balance, carbohydrate metabolism and immune response of gills (dsEGFP-Vp vs dsHIFn-1α-Vp). In dsHIFn-1α-Vp group, nicotinic acid and nicotinamide metabolism and arachidonic acid metabolism were significantly upregulated, while the pentose phosphate pathway was significantly downregulated. In addition, more immune DEGs, including C-type lectins, NLRs, penaeidins, ALFs, prophenoloxidases and kazal-type proteinase inhibitors were highly expressed in the dsHIFn-1α-Vp group. Notably, key antioxidant and immune parameters, including copper/zinc superoxide dismutase (SOD), peroxidase (POD) and prophenoloxidase (PO) activities, as well as total glutathione levels, were reduced in LvHIFn-1α -knockdown shrimp. Our findings suggest that knockdown of LvHIFn-1α induced oxidative damage, altered glycolysis and exacerbated inflammation in gills, thereby facilitating V. parahaemolyticus infection. • Multi-omics analysis was performed to study the effect of LvHIFn-1α knockdown on Vibrio infection. • LvHIFn-1α knockdown caused dysregulation in glycolysis, glutathione metabolism and arachidonic acid metabolism. • LvHIFn-1α knockdown exacerbated changes in redox balance, carbohydrate metabolism and immune response after Vibrio infection. • The changes in immune metabolism of LvHIFn-1α -interfered shrimp facilitated Vibrio infection.