Amplifying STING Activation and Alleviating Immunosuppression through a Mn2+-Based Metal-Organic Framework Nanosystem for Synergistic Cancer Therapy.

The field of immunotherapy, particularly immune checkpoint blockade (ICB), holds immense potential in mitigating the progression of cancer. However, the challenges of insufficient tumor antigen production and the immunosuppressive state in the tumor microenvironment substantially impede patients from deriving benefits. In this research, we present a tumor-microenvironment-modulation manganese-based nanosystem, PEG-MnMOF@PTX, aiming to improve the responsiveness of ICB. Under acidic conditions, the released Mn2+ accomplishes multiple objectives. It generates toxic hydroxyl radicals (•OH), together with the released paclitaxel (PTX), inducing immunogenic cell death of tumor cells and normalizing tumor blood vessels. Concurrently, it facilitates the in situ generation of oxygen (O2) from hydrogen peroxide (H2O2), ameliorating the microenvironmental immunosuppression and increasing the efficacy of immunotherapy. In addition, this study demonstrates that PEG-MnMOF@PTX can promote the maturation of dendritic cells and augment the infiltration of cytotoxic T lymphocytes through activation of the cyclic guanosine 5'-monophosphate-adenosine 5'-monophosphate synthase (cGAS) and interferon gene stimulator (STING) pathways, namely cGAS-STING pathways, thereby heightening the sensitivity to ICB immunotherapy. The findings of this study present a novel paradigm for the progress in cancer immunotherapy.

PqsA mutation-mediated enhancement of phage-mediated combat against Pseudomonas aeruginosa.

Phage therapy is a potential approach in the biocontrol of foodborne pathogens. However, the emergence of phage resistance and the narrow host range of most phage isolates continue to limit the antimicrobial efficacy of phages. Here, we investigated the potential of the pqsA gene, encoding the anthranilate-CoA ligase enzyme, as an adjuvant for phage therapy. The knockout of the pqsA gene significantly enhanced the bactericidal effect of phages vB_Pae_QDWS and vB_Pae_S1 against Pseudomonas aeruginosa. Under phage infection pressure, the growth of the PaΔpqsA was significantly inhibited within 8 h compared to the wild-type PAO1. Furthermore, we found that altering phage adsorption is not how PaΔpqsA responds to phage infection. Although pqsA represents a promising target for enhancing phage killing, it may not be applicable to all phages, such as types vB_Pae_W3 and vB_Pae_TR. Our findings provide new material reserves for the future design of novel phage-based therapeutic strategies.

Self-Reinforced Bimetallic Mito-Jammer for Ca2+ Overload-Mediated Cascade Mitochondrial Damage for Cancer Cuproptosis Sensitization.

Overproduction of reactive oxygen species (ROS), metal ion accumulation, and tricarboxylic acid cycle collapse are crucial factors in mitochondria-mediated cell death. However, the highly adaptive nature and damage-repair capabilities of malignant tumors strongly limit the efficacy of treatments based on a single treatment mode. To address this challenge, a self-reinforced bimetallic Mito-Jammer is developed by incorporating doxorubicin (DOX) and calcium peroxide (CaO2) into hyaluronic acid (HA) -modified metal-organic frameworks (MOF). After cellular, Mito-Jammer dissociates into CaO2 and Cu2+ in the tumor microenvironment. The exposed CaO2 further yields hydrogen peroxide (H2O2) and Ca2+ in a weakly acidic environment to strengthen the Cu2+-based Fenton-like reaction. Furthermore, the combination of chemodynamic therapy and Ca2+ overload exacerbates ROS storms and mitochondrial damage, resulting in the downregulation of intracellular adenosine triphosphate (ATP) levels and blocking of Cu-ATPase to sensitize cuproptosis. This multilevel interaction strategy also activates robust immunogenic cell death and suppresses tumor metastasis simultaneously. This study presents a multivariate model for revolutionizing mitochondria damage, relying on the continuous retention of bimetallic ions to boost cuproptosis/immunotherapy in cancer.

Decomposable Nanoagonists Enable NIR-Elicited cGAS-STING Activation for Tandem-Amplified Photodynamic-Metalloimmunotherapy.

Activation of the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway has emerged as an efficient strategy to improve the therapeutic outcomes of immunotherapy. However, the "constantly active" mode of current STING agonist delivery strategies typically leads to off-target toxicity and hyperimmunity. To address this critical issue, herein a metal-organic frameworks-based nanoagonist (DZ@A7) featuring tumor-specific and near-infrared (NIR) light-enhanced decomposition is constructed for precisely localized STING activation and photodynamic-metalloimmunotherapy. The engineered nanoagonist enabled the generation of mitochondria-targeted reactive oxygen species under NIR irradiation to specifically release mitochondrial DNA (mtDNA) and inhibit the repair of nuclear DNA via hypoxia-responsive drugs. Oxidized tumor mtDNA serves as an endogenous danger-associated molecular pattern that activates the cGAS-STING pathway. Concurrently, NIR-accelerated zinc ions overloading in cancer cells further enhance the cGAS enzymatic activity through metalloimmune effects. By combining the synergistically enhanced activation of the cGAS-STING pathway triggered by NIR irradiation, the engineered nanoagonist facilitated the maturation of dendritic cells and infiltration of cytotoxic T lymphocytes for primary tumor eradication, which also established a long-term anti-tumor immunity to suppress tumor metastasis. Therefore, the developed nanoagonist enabled NIR-triggered, agonist-free, and tandem-amplified activation of the cGAS-STING pathway, thereby offering a distinct paradigm for photodynamic-metalloimmunotherapy.

Hepatitis B virus-mediated sodium influx contributes to hepatic inflammation via synergism with intrahepatic danger signals.

The NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome has been involved in the pathogenesis of various chronic liver diseases. However, its role in hepatitis B virus (HBV)-associated hepatitis remains unknown. Here we demonstrate the synergistic effect of HBV with potential intrahepatic danger signals on NLRP3 inflammasome activation. HBV exposure at the appropriate temporal points enhances potassium efflux-dependent NLRP3 inflammasome activation in macrophages and also increases NLRP3 inflammasome-mediated inflammation in HBV-transgenic mouse model. HBV-mediated synergism with intrahepatic signals represented by ATP molecules on NLRP3 activation was observed via relevance analysis, confocal microscopy, and co-immunoprecipitation, and its effector cytokines exhibit positive associations with hepatic inflammation in patients with severe hepatitis B. Furthermore, the synergism of HBV on NLRP3 inflammasome activation owes to increased sodium influx into macrophages. Our data demonstrate that HBV contributes to hepatic inflammation via sodium influx-dependent synergistic activation of NLRP3 inflammasome, which provides a deeper understanding of immune pathogenesis in HBV-associated hepatitis.

[Preparation and properties of hydrogels loaded with phage endolysin Lys84].

This study investigated the application of poly(N-isopropylacrylamide)-based interpenetrating network temperature-sensitive hydrogels (notation: IPNT) as the delivery vehicle for phage endolysin Lys84 and the potential of drug-loaded hydrogels as antimicrobial materials. Interpenetrating network temperature-sensitive hydrogels were prepared by free radical polymerization of sodium alginate and N-isopropylacrylamide. Drug-loaded hydrogels (IPNT-Lys84) were obtained by dry soaking method with the endolysin Lys84 of Staphylococcus aureus phage. The physical properties of the hydrogels with and without drug loading were characterized by infrared spectroscopy, scanning electron microscopy, and differential scanning calorimetry. The swelling and deswelling of the hydrogels as well as the release of endolysin Lys84 were investigated. Moreover, the antibacterial properties of IPNT-Lys84 hydrogels at different temperatures and concentrations of the drug solution were studied. The results showed that IPNT-Lys84 hydrogel had uniform pores and a low critical solubility temperature (LCST) of 32 ℃. The equilibrium swelling of the hydrogel was 30 g/g, and the water loss rate was 88% upon deswelling. The release rate of endolysin reached more than 70% within 6 h at 37 ℃. The bactericidal rate of IPNT-Lys84 hydrogel was over 99.9%. The research results showed the feasibility of using IPNT to deliver the endolysin Lys84, and IPNT-Lys84 hydrogel might be an effective antimicrobial material against multi-drug resistant Staphylococcus aureus.

Complete genome analysis and biological characterization of a novel phage vB_CP_qdyz_P5 with lytic activity against Clostridium perfringens.

Clostridium perfringens, a common foodborne pathogen, exhibit high-stress resistance. The prevailing reliance on antibiotics in the farming industry for its prevention and control has led to increasing concerns over antibiotic residue and bacterial resistance. Bacteriophages that possess specific lytic activity against C. perfringens are of significant interest. Here, a novel C. perfringens phage, named vB_CP_qdyz_P5, was isolated and characterized. The phage displayed high stability at temperatures below 70 °C and pH levels ranging from 4 to 12. Genome analysis revealed that vB_CP_qdyz_P5 has a double-stand DNA of 18,888 bp with a G + C composition of 28.8%. Among the 27 identified opening reading frames (ORFs), eight were found to be functional genes. BLASTn analysis showed that vB_CP_qdyz_P5 is closely related to phage DCp1, with a genome homology coverage of 83%. Phylogenetic analysis indicated that vB_CP_qdyz_P5 may be a novel phage of the family Guelinviridae, Susfortunavirus. This study provides important preliminary information for further research on the potential use of vB_CP_qdyz_P5 in protecting against C. perfringens and maintaining intestinal health.

Quorum sensing autoinducers AHLs protect Shewanella baltica against phage infection.

Quorum sensing (QS) plays an important role in phage-host interactions. Shewanella baltica can't produce the N-acyl-homoserine lactones (AHLs) signal molecules but can eavesdrop on exogenous AHLs through its LuxR receptor. However, no clear evidence exists regarding the involvement of AHLs-mediated QS systems in S. baltica in regulating phage infection. Here, we report that AHLs modulated the phage resistance of S. baltica OS155. Specifically, we characterized a S. baltica phage vB_Sb_QDWS and preliminarily identified that lipopolysaccharide (LPS) is an important receptor for phage vB_Sb_QDWS. AHLs could protect S. baltica against phage infection by decreasing LPS-mediated phage adsorption. The expression of genes galU and tkt, which are essential for LPS synthesis, down-regulated significantly in response to AHLs autoinducers. Our finding confirms the important roles of QS in virus-host interactions and would be helpful to develop novel phage strategies for food spoilage control.

Genome­wide identification and characterization of miR396 family members and their target genes GRF in sorghum (Sorghum bicolor (L.) moench).

MicroRNAs (miRNAs) widely participate in plant growth and development. The miR396 family, one of the most conserved miRNA families, remains poorly understood in sorghum. To reveal the evolution and expression pattern of Sbi-miR396 gene family in sorghum, bioinformatics analysis and target gene prediction were performed on the sequences of the Sbi-miR396 gene family members. The results showed that five Sbi-miR396 members, located on chromosomes 4, 6, and 10, were identified at the whole-genome level. The secondary structure analysis showed that the precursor sequences of all five Sbi-miR396 potentially form a stable secondary stem-loop structure, and the mature miRNA sequences were generated on the 5' arm of the precursors. Sequence analysis identified the mature sequences of the five sbi-miR396 genes were high identity, with differences only at the 1st, 9th and 21st bases at the 5' end. Phylogenetic analysis revealed that Sbi-miR396a, Sbi-miR396b, and Sbi-miR396c were clustered into Group I, and Sbi-miR396d and Sbi-miR396e were clustered into Group II, and all five sbi-miR396 genes were closely related to those of maize and foxtail millet. Expression analysis of different tissue found that Sbi-miR396d/e and Sbi-miR396a/b/c were preferentially and barely expressed, respectively, in leaves, flowers, and panicles. Target gene prediction indicates that the growth-regulating factor family members (SbiGRF1/2/3/4/5/6/7/8/10) were target genes of Sbi-miR396d/e. Thus, Sbi-miR396d/e may affect the growth and development of sorghum by targeting SbiGRFs. In addition, expression analysis of different tissues and developmental stages found that all Sbi-miR396 target genes, SbiGRFs, were barely expressed in leaves, root and shoot, but were predominantly expressed in inflorescence and seed development stage, especially SbiGRF1/5/8. Therefore, inhibition the expression of sbi-miR396d/e may increase the expression of SbiGRF1/5/8, thereby affecting floral organ and seed development in sorghum. These findings provide the basis for studying the expression of the Sbi-mir396 family members and the function of their target genes.

Characterization of a novel phage vB_Pae_HB2107-3I that infects Pseudomonas aeruginosa.

Bacteriophages are potential antibiotic substitutes for the treatment of antibiotic resistant bacteria. Here, we report the genome sequences of a double-stranded DNA podovirus vB_Pae_HB2107-3I against clinical multi-drug resistant Pseudomonas aeruginosa. Phage vB_Pae_HB2107-3I remained stable over a wide range of temperatures (37-60 °C) and pH values (pH 4-12). At MOI of 0.01, the latent period of vB_Pae_HB2107-3I was 10 min, and the final titer reached about 8.1 × 109 PFU/mL. The vB_Pae_HB2107-3I genome is 45,929 bp, with an average G + C content of 57%. A total of 72 open reading frames (ORFs) were predicted, of which 22 ORFs have a predicted function. Genome analyses confirmed the lysogenic nature of this phage. Phylogenetic analysis revealed that phage vB_Pae_HB2107-3I was a novel member of Caudovirales infecting P. aeruginosa. The characterization of vB_Pae_HB2107-3I enrich the research on Pseudomonas phages and provide a promising biocontrol agent against P. aeruginosa infections.

Tn5 Transposon-based Mutagenesis for Engineering Phage-resistant Strains of Escherichia coli BL21 (DE3).

Escherichia coli is a preferred strain for recombinant protein production, however, it is often plagued by phage infection during experimental studies and industrial fermentation. While the existing methods of obtaining phage-resistant strains by natural mutation are not efficient enough and time-consuming. Herein, a high-throughput method by combining Tn5 transposon mutation and phage screening was used to produce Escherichia coli BL21 (DE3) phage-resistant strains. Mutant strains PR281-7, PR338-8, PR339-3, PR340-8, and PR347-9 were obtained, and they could effectively resist phage infection. Meanwhile, they had good growth ability, did not contain pseudolysogenic strains, and were controllable. The resultant phage-resistant strains maintained the capabilities of producing recombinant proteins since no difference in mCherry red fluorescent protein expression was found in phage-resistant strains. Comparative genomics showed that PR281-7, PR338-8, PR339-3, and PR340-8 mutated in ecpE, nohD, nrdR, and livM genes, respectively. In this work, a strategy was successfully developed to obtain phage-resistant strains with excellent protein expression characteristics by Tn5 transposon mutation. This study provides a new reference to solve the phage contamination problem.

Endowing Porphyrinic Metal-Organic Frameworks with High Stability by a Linker Desymmetrization Strategy.

The fabricating of metal-organic frameworks (MOFs) that integrate high stability and functionality remains a long-term pursuit yet a great challenge. Herein, we develop a linker desymmetrization strategy to construct highly stable porphyrinic MOFs, namely, USTC-9 (USTC represents the University of Science and Technology of China), presenting the same topological structure as the well-known PCN-600 that readily loses crystallinity in air or upon conventional activation. For USTC-9, the involved porphyrinic linker (TmCPP-M) with carboxylate groups located in the meta-position presents a chair-shaped conformation with lower C2h symmetry than that (D4h) of the common porphyrinic carboxylate (TCPP) linker in PCN-600. As a result, the wrinkled and interlocked linker arrangements collectively contribute to the remarkable stability of USTC-9. Given the high stability and porosity as well as Lewis acidity, USTC-9(Fe) demonstrates its excellent performance toward catalytic CO2 cycloaddition with diverse epoxides at moderate temperature and atmospheric pressure.

Phage resistance of Salmonella enterica obtained by transposon Tn5-mediated SefR gene silent mutation.

Salmonella enterica contamination is a primary cause of global food poisoning. Using phages as bactericidal alternatives to antibiotics could confront the issue of drug resistance. However, the problem of phage resistance, especially mutant strains with multiple phage resistance, is a critical barrier to the practical application of phages. In this study, a library of EZ-Tn5 transposable mutants of susceptible host S. enterica B3-6 was constructed. After the infestation pressure of a broad-spectrum phage TP1, a mutant strain with resistance to eight phages was obtained. Analysis of the genome resequencing results revealed that the SefR gene was disrupted in the mutant strain. The mutant strain displayed a reduced adsorption rate of 42% and a significant decrease in swimming and swarming motility, as well as a significantly reduced expression of the flagellar-related FliL and FliO genes to 17% and 36%, respectively. An uninterrupted form of the SefR gene was cloned into vector pET-21a (+) and used for complementation of the mutant strain. The complemented mutant exhibited similar adsorption and motility as the wild-type control. These results suggest that the disrupted flagellar-mediated SefR gene causes an adsorption inhibition, which is responsible for the phage-resistant phenotype of the S. enterica transposition mutant.

Characterization of the newly isolated phage Y3Z against multi-drug resistant Cutibacterium acnes.

Cutibacterium acnes (C. acnes) is a symbiotic bacterium that plays an important role in the formation of acn e inflammatory lesions. As a common component of the acne microbiome, C. acnes phages have the potential to make a significant contribution to treating antibiotic-resistant strains of C. acnes. However, little is known about their genetic composition and diversity. In this study, a new lytic phage, Y3Z, infecting C. acne, was isolated and characterized. Electron microscopy analysis revealed this phage is a siphovirus. Phage Y3Z is composed of 29,160 bp with a GC content of 56.32%. The genome contains 40 open reading frames, 17 of which had assigned functions, while no virulence-related genes, antibiotic resistance genes or tRNA were identified. The one-step growth curve showed the burst size was 30 PFU (plaque-forming unit)/cell. And it exhibited tolerance over a broad range of pH and temperature ranges. Phage Y3Z could infect and lyse all C. acnes isolates tested, though the host range of PA6 was restricted to C. acnes. Based on the phylogenetic and comparative genomic analyses, Y3Z may represent a new siphovirus infecting C. acnes. Characterization of Y3Z will enrich our knowledge about the diversity of C. acnes phages and provide a potential arsenal for thetreatment of acne infection.

Ni-doped MoS2 embedded in natural wood containing porous cellulose for piezo-catalytic degradation of tetracycline.

Wood is a natural material with low cost and easy recovery, which porous, layered, excellent structure and mechanical properties make it possible to apply in wastewater treatment. We have successfully grown MoS2 on natural wood containing porous cellulose and introduced the high conductivity circuit path provided by Ni nanoparticles to construct a new piezoelectric three-dimensional wood block for the efficient degradation of tetracycline. Ni/MoS2/Wood exhibited excellent piezo-catalytic degradation performance, and the degradation rate of tetracycline reached 95.96 % (k = 0.0411 min-1) under ultrasonic vibration. After 5 cycles, the degradation rate still reached 90.20 %. In addition, Ni/MoS2/Wood was used as the reactor filler to degrade tetracycline through piezoelectric response triggered by hydrodynamic force, and the degradation rate reached 90.27 % after 60 min. Further, the mechanism and the possible degradation pathways of tetracycline degradation were proposed. This low-cost, recyclable and stable three-dimensional wood block piezoelectric material provides a new idea for the practical application of wastewater treatment.

Oxygen-carrying nanoplatform to reprogram tumor immunosuppressive microenvironment and enhance photothermal-immunotherapy.

Immunotherapy shows great promise on treating tumors. However, insufficient antigen exposure and immunosuppressive tumor microenvironment (TME) caused by hypoxia impose a serial of constraints on the therapeutic efficacy. In this study, we developed an oxygen-carrying nanoplatform loaded with perfluorooctyl bromide (PFOB, a second-generation of perfluorocarbon-based blood substitute), IR780 (a photosensitizer) and imiquimod (R837, an immune adjuvant) to reprogram immunosuppressive TME and reinforce photothermal-immunotherapy. The obtained oxygen-carrying nanoplatforms (abbreviated as IR-R@LIP/PFOB) show highly efficient oxygen release behavior and excellent hyperthermia performance upon laser irradiation, thus achieving the attenuation of the inherent tumor hypoxia and the exposure of tumor associated antigens in situ, and transforming the immunosuppressive TME to an immunosupportive one. We found that the photothermal therapy of IR-R@LIP/PFOB together with anti-programmed cell death protein-1 (anti-PD-1) would elicit a robust antitumor immunity by increasing the tumor-infiltrating frequencies of cytotoxic CD8+ T cells and tumoricidal M1-phenotype macrophages, while reducing immunosuppressive M2-phenotype macrophages and regulatory T cells (Tregs). This study presents these oxygen-carrying IR-R@LIP/PFOB nanoplatforms are potent in removing some negative impacts of immunosuppressive TME caused by hypoxia, and suppressing tumor growth by initiating antitumor immune responses, especially in combination with anti-PD-1 immunotherapy.

Genomic analysis and biological properties of the novel Serratia liquefaciens phage vB_SlqM_MQ-4.

A novel lytic Serratia liquefaciens phage, named vB_SlqM_MQ-4, was isolated from sewage. BLASTn analysis showed that the genome sequence of phage vB_SlqM_MQ-4 shared only 15% query coverage with that of Escherichia phage vB_EcoM-ep3, with 80.52% identity. Genomic analysis demonstrated that phage vB_SlqM_MQ-4 has a 43,534-bp dsDNA genome with 56% GC content and might be a member of a new genus in the order Caudoviricetes. Moreover, vB_SlqM_MQ-4 exhibited strong lytic performance with a short latent period (10 min) and a high burst size (267 PFU per cell) as well as a wide range of thermal (below 70 ℃) and pH tolerance (pH 4-12).

NIR Activated Multimodal Therapeutics Based on Metal-Phenolic Networks-Functionalized Nanoplatform for Combating against Multidrug Resistance and Metastasis.

Multidrug resistance (MDR) and metastasis in cancer have become increasingly serious problems since antitumor efficiency is greatly restricted by a single therapeutic modality and the insensitive tumor microenvironment (TME). Herein, metal-phenolic network-functionalized nanoparticles (t-P@TFP NPs) are designed to realize multiple therapeutic modalities and reshape the TME from insensitive to sensitive under multimodal imaging monitoring. After a single irradiation, a near-infrared laser-activated multistage reaction occurs. t-P@TFP NPs trigger the phase transition of perfluoropentane (PFP) to release tannic acid (TA)/ferric ion (Fe3+ )-coated paclitaxel (PTX) and cause hyperthermia in the tumor region to efficiently kill cancer cells. Additionally, PTX is released after the disassembly of the TA-Fe3+ film by the abundant adenosine triphosphate (ATP) in the malignant tumor, which concurrently inhibits ATP-dependent drug efflux to improve sensitivity to chemotherapeutic agents. Furthermore, hyperthermia-induced immunogenic cell death (ICD) transforms "cold" tumors into "hot" tumors with the assistance of PD-1/PD-L1 blockade to evoke antitumor immunogenicity. This work carefully reveals the mechanisms underlying the abilities of these multifunctional NPs, providing new insights into combating the proliferation and metastasis of multidrug-resistant tumors.

Pseudomonas aeruginosa Resists Phage Infection via Eavesdropping on Indole Signaling.

Phage therapy is challenged by the frequent emergence of bacterial resistance to phages. As an interspecies signaling molecule, indole plays important roles in regulating bacterial behaviors. However, it is unclear whether indole is involved in the phage-bacterium interactions. Here, we report that indole modulated phage resistance of Pseudomonas aeruginosa PAO1. Specifically, we found that the type IV pilus (T4P) acts as an important receptor for P. aeruginosa phages vB_Pae_S1 and vB_Pae_TR, and indole could protect P. aeruginosa against phage infection via decreasing the T4P-mediated phage adsorption. Further investigation demonstrated that indole downregulated the expression of genes pilA, pilB, and pilQ, which are essential for T4P assembly and activity. Indole inhibits phage attacks, but our data suggest that indole functions not through interfering with the AHL-based QS pathway, although las quorum sensing (QS) of P. aeruginosa PAO1 were reported to promote phage infection. Our finding confirms the important roles of indole in virus-host interactions, which will provide important enlightenment in promoting phage therapy for P. aeruginosa infections. IMPORTANCE Our finding is significant with respect to the study of the interactions between phage and host. Although the important roles of indole in bacterial physiology have been revealed, no direct examples of indole participating in phage-host interactions were reported. This study reports that indole could modulate the phage resistance of indole-nonproducing Pseudomonas aeruginosa PAO1 through inhibition of phage adsorption mechanism. Our finding will be significant for guiding phage therapy and fill some gaps in the field of phage-host interactions.

Development of the phage lysin-loaded liposomes as preservatives for live clams.

Exogenous applications of phage lysins against Vibrio parahaemolyticus (V. parahaemolyticus) are a challenge due to the gram-negative bacteria outer membrane barrier. This study aimed to improve the antibacterial effect of V. parahaemolyticus phage lysin Lysqdvp001 (Lys), the best-characterized lysin with lytic activity against multiple species of Vibrios, by using liposome delivery. Various kinds of Lys-loaded liposome (Lys-lip) systems were designed and tested. The antibacterial activities of cationic guar gum (CGG) containing liposomes were much higher than the other liposomes, causing >5 log10CFU/mL of reductions of V. parahaemolyticus in buffer and severely damaging the bacterial cell structure. Moreover, some CGG liposome formulations retained high antibacterial effect after both 60-80 °C heat treatments and freeze-drying. Besides, the most stable liposome formulation killed 99 % of V. parahaemolyticus in the seawater with live clams, and its depuration rate against the bacterial contaminated clams also reached 99 %.