Hexosamine biosynthesis drives hemocyanin O-GlcNAcylation to potentiate antibacterial immunity in shrimp

  • J Biol Chem. 2026 May 28;302(7):113213. doi: 10.1016/j.jbc.2026.113213.
Qian Feng  1 ,  Maoshuai Fu  2 ,  Wei Wang  2 ,  Tingchu Wu  2 ,  Junjie Nie  1 ,  Zhihong Zheng  2 ,  Yongzhen Zhao  3 ,  Jude Juventus Aweya  4 ,  Yueling Zhang  5
Affiliations
  • 1. Institute of Marine Sciences and Guangdong Provincial Key Laboratory of Marine Biotechnology, Shantou University, Shantou, China; Department of Medical Laboratory and Department of Reproductive Medicine, Luohu Clinical College of Shantou University Medical College, Shantou University, Shantou, China.
  • 2. Institute of Marine Sciences and Guangdong Provincial Key Laboratory of Marine Biotechnology, Shantou University, Shantou, China.
  • 3. Guangxi Academy of Fishery Sciences, Guangxi Key Laboratory of Aquatic Genetic Breeding and Healthy Aquaculture, Nanning, China.
  • 4. Institute of Marine Sciences and Guangdong Provincial Key Laboratory of Marine Biotechnology, Shantou University, Shantou, China; College of Ocean Food and Biological Engineering, Jimei University, Xiamen, Fujian, China; Department of Food and Human Nutritional Sciences, University of Manitoba, Winnipeg, Manitoba, Canada; The Canadian Centre for Agri-Food Research in Health and Medicine, St Boniface Hospital Albrechtsen Research Centre, Winnipeg, Manitoba, Canada. Electronic address: [email protected].
  • 5. Institute of Marine Sciences and Guangdong Provincial Key Laboratory of Marine Biotechnology, Shantou University, Shantou, China. Electronic address: [email protected].
PMID: 42214671 DOI: 10.1016/j.jbc.2026.113213
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.

Keywords
O-GlcNAcylation; Penaeus vannamei; antibacterial immunity; hemocyanin; hexosamine biosynthetic pathway; host-pathogen interaction; metabolic reprogramming; post-translational modification.
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