Fangyi Chen

Psychrotrophic Pseudomonas are the main spoilage bacteria in refrigerated aquatic products, but conventional preservatives are limited and fail to address the inflammatory risk of Pseudomonas lipopolysaccharide. We identified and synthesized Sparadin118–140, a 23-residue peptide within the Sparadin protein from Scylla paramamosain. It showed potent bactericidal activity against three Pseudomonas species via membrane disruption, retained activity at refrigeration temperature, and adopted an α-helical conformation. It inhibited biofilm formation and disrupted established biofilms. The peptide also suppressed P. aeruginosa LPS-induced inflammation in macrophages and zebrafish, reducing pro-inflammatory cytokines while upregulating IL-10, and showed favorable biocompatibility and stability under neutral pH, refrigeration, and thermal processing conditions. In preservation assays, it inhibited bacterial growth, retarded protein hydrolysis and lipid oxidation, and extended the shelf life of refrigerated tilapia fillets, with effects comparable to potassium sorbate. Thus, Sparadin118–140 is a multifunctional natural biopreservative against Pseudomonas spoilage and LPS-associated inflammatory hazards.

Fusarium graminearum, the causal agent of Fusarium head blight, poses a serious threat to global cereal production and food safety due to severe mycotoxin contamination. Here, we report that Spampcin_56–86, a marine antimicrobial peptide from Scylla paramamosain, exhibits potent antifungal activity by rapidly inhibiting spore germination and mycelial growth of F. graminearum. Mechanistically, the peptide disrupts fungal cell membrane integrity, leading to extensive leakage of intracellular contents. Concurrently, it induces lethal reactive oxygen species accumulation and membrane lipid peroxidation, triggering a compensatory chitin stress response. Importantly, Spampcin_56–86 markedly suppresses deoxynivalenol (DON) biosynthesis through transcriptional interference with the TRI gene cluster. In planta assays further demonstrate that the peptide delivers robust therapeutic protection against foliar infections and effectively prevents wheat grain spoilage during storage, without causing phytotoxicity. Collectively, these findings highlight Spampcin_56–86 as a promising, safe, and dual-action natural biocontrol agent for managing F. graminearum and mitigating mycotoxin risks.

Edwardsiella tarda is a significant pathogen in aquaculture, causing severe systemic infections and considerable economic losses worldwide. The limited efficacy of current treatments and the emergence of multidrug-resistant strains underscore the urgent need for novel antimicrobial strategies. Antimicrobial peptides have garnered increasing interest due to their broad-spectrum activity and low risk of resistance development. In this study, we identified a novel immune-related gene from the mudskipper Boleophthalmus pectinirostris , named Pecbloodin , which encodes a mature peptide of 67 amino acids. A truncated peptide derived from this sequence, Pecbloodin _18-37 , exhibited broad-spectrum antibacterial activity, high thermal stability, and tolerance to sodium ions. Functional assays demonstrated that Pecbloodin _18-37 exerts rapid bactericidal effects by compromising bacterial membrane integrity, inducing cellular content leakage, and triggering endogenous reactive oxygen species accumulation. Furthermore, it effectively inhibited bacterial biofilm formation and did not promote resistance under prolonged exposure. Importantly, in vivo experiments using an E. tarda -infected mudskipper model revealed that Pecbloodin _18-37 significantly improved host survival and modulated the immune response. Overall, Pecbloodin _18-37 shows great potential as a promising alternative to conventional antibiotics for the control of E. tarda infections in aquaculture, addressing the pressing issue of antibiotic resistance. IMPORTANCE: Edwardsiella tarda is an urgent threat to global aquaculture. We mined the mudskipper Boleophthalmus pectinirostris genome for antimicrobial peptide and identified Pecbloodin _18-37 , a 20-aa thermostable peptide that rapidly permeabilizes bacterial membranes, elicits intracellular reactive oxygen species, blocks biofilm formation, and does not select for resistance. In E. tarda -challenged fish, a single dose reduced mortality by 25% and restored immune homeostasis. The peptide is readily synthesized and feed-compatible, providing an immediate, resistance-proof substitute for conventional antibiotics in fish farming.

Frequent outbreaks of eel "mucus sloughing and hemorrhagic septicemia disease" caused by Anguillid herpesvirus 1 (AngHV) are a major epidemic in both wild and farmed eels. This virus has garnered global attention due to heavy losses on eel farms and the lack of protective vaccines or effective drugs, highlighting the urgent need for potent antiviral agents. In this study, we revealed a hepcidin homolog LJ-hep2 from Japanese seabass (Lateolabrax japonicus) can bind to AngHV and impede viral entry into cells. LJ-hep2 could directly destroy the viral envelope and showed a higher anti-AngHV activity than AA-hep (a hepcidin homolog cloned from Anguilla anguilla). It was found that the destruction of viral structure by LJ-hep2 was related to the binding of the peptide to AngHV envelope protein ORF51, and the two amino acid residues at the N-terminus of the peptide (lysine and phenylalanine) might play a key role. Comparative antiviral experiments with mutated LJ-hep2 (LJ-hep2_A4A5) and multi-species hepcidin further confirmed this finding and demonstrated that these two amino acids were indispensable in the inhibition of AngHV infection by LJ-hep2. In an established eel immersion infection model, LJ-hep2 treatment reduced viral accumulation in tissues, inhibited horizontal transmission, alleviated skin lesions, and improved eel survival. Taken together, this study suggests that LJ-hep2 could inhibit AngHV infection in vitro and in vivo, and identify ORF51 as a potential target for the development of anti-AngHV drugs.

The escalating threat of antimicrobial resistance (AMR) has created an urgent need for alternative therapeutic strategies beyond traditional antibiotics. In this study, we identified a new antimicrobial peptide, Boleokidin_39-61, encoded by the immune-regulated gene Boleokidin in the amphibious fish Boleophthalmus pectinirostris. Notably, the expression of this gene was significantly upregulated in the liver and spleen following Edwardsiella tarda infection. Boleokidin_39-61 exhibited broad-spectrum antibacterial activity against Gram-positive and Gram-negative bacteria, including multidrug-resistant strains. Mechanistic analyses showed that the peptide kills bacteria by disrupting membrane integrity, inhibits biofilm formation, and does not induce resistance under prolonged exposure. Cytotoxicity assays revealed no significant toxicity toward mammalian cells or erythrocytes at antimicrobial concentrations. Importantly, in vivo infection studies using both zebrafish and mice models confirmed the peptide's therapeutic efficacy, demonstrating its ability to reduce bacterial burden and modulate host inflammatory responses. Collectively, these findings highlight Boleokidin_39-61 as a promising AMP candidate with potent antimicrobial and immunomodulatory properties, offering the potential for application in aquaculture and biomedical fields.

病原菌耐药性问题严重影响着全球人类健康，寻找抗生素的有效替代品已迫在眉睫。本课题组自2001年以来一直致力于海洋生物新型抗菌肽的研究与利用工作，发现并鉴定了百余种新型抗菌肽，其中筛选确定了多种体外高效抗临床分离的多重耐药性病原菌的抗菌肽，并通过多种耐药性病原菌小鼠感染模型证明了4种海洋动物新型抗菌肽在体内具有显著的抗感染作用。本文将简要总结这些源于海洋的新型抗菌肽的发现、筛选、体内外活性评价及作用机制等诸方面的研究成果，为探索其在临床上抗耐药性菌感染的应用提供科学依据，并为研发可替代抗生素的有效药物提供理论依据和技术支撑。