ArticleThe Journal of biological chemistry2026
Hexosamine biosynthesis drives hemocyanin O-GlcNAcylation to potentiate antibacterial immunity in shrimp.
Article in The Journal of biological chemistry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Post-translational modifications (PTMs) are key regulators of immune responses; however, their roles in invertebrate immunity remain poorly defined. Here, we show that Penaeus vannamei employs O-GlcNAcylation, a dynamic PTM controlled by the hexosamine biosynthetic pathway (HBP), to enhance antibacterial defense. Bacterial infection induces metabolic reprogramming in hemocytes, upregulating HBP enzymes, and promoting O-GlcNAcylation of hemocyanin (PvHMC) through O-GlcNAc transferase (PvOGT). Site-specific modification of the PvHMC large subunit at Thr584 enhances its conformational stability and interaction with bacterial pathogen-associated molecular patterns, including lipopolysaccharide and peptidoglycan, thereby increasing bacterial binding, agglutination, and killing. Disruption of HBP flux or OGT activity reduces hemocyanin O-GlcNAcylation and impairs bacterial clearance, whereas inhibition of O-GlcNAcase enhances O-GlcNAcylation and antibacterial efficacy. Together, these findings identify HBP-driven O-GlcNAcylation as a metabolic-immune regulatory axis in shrimp and establish hemocyanin O-GlcNAcylation as a key mechanism underlying effective innate antibacterial defense, with potential implications for disease control in aquaculture.
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