Luminescence regulator (LuxR) modulates Vibrio harveyi pathogenicity and reshapes the transcriptional and splicing landscape in Penaeus vannamei

The quorum sensing regulator LuxR is central to Vibrio harveyi virulence, but its role in modulating host responses remains unclear. In this study, we investigated the virulence attenuation of a luxR deletion mutant (ΔluxR) in Penaeus vannamei and characterized the host response using histopathological, transcriptomic, and alternative splicing analyses. Virulence assays showed that the LD50 of ΔluxR (3.87 × 105 CFU/g) was 60-fold higher than that of the wild-type (WT) strain (6.35 × 103 CFU/g), confirming LuxR is essential for full virulence. Histopathology revealed that ΔluxR infection caused delayed lesion development, reduced necrosis, and accelerated regeneration compared to WT infection. Transcriptomic analysis identified only 237 differentially expressed genes (DEGs) across three time points. Notably, at 6 hours post-infection, three pattern recognition receptor genes were upregulated exclusively in ΔluxR-infected shrimp, suggesting LuxR facilitates immune evasion by suppressing early host recognition. Gene set enrichment analysis revealed distinct metabolic dynamics: WT infection rapidly activated ribosome biogenesis and oxidative phosphorylation, whereas ΔluxR infection promoted anabolic pathway restoration by 24 hours. Differential alternative splicing (DAS) analysis identified 1,136 genes with splicing changes, far exceeding the number of DEGs. Protein-protein interaction network analysis of 336 merged DAS genes revealed 11 hub proteins, including ribosomal subunits, aminoacyl-tRNA synthetases, THO complex subunit 4, and splicing factor 1B. Together, these findings demonstrate that LuxR profoundly shapes both host transcriptional and splicing landscapes, highlighting alternative splicing in ribosomal and RNA processing genes as a previously underappreciated immune regulatory mechanism and offering new targets for anti-virulence therapies.