Vibrio vulnificus (V. vulnificus) is a marine bacterium that can cause sepsis, characterized by rapid progression of infection and high clinical mortality rates. However, many healthcare workers lack systematic understanding of V. vulnificus infections and practical experience in the prevention and control of V. vulnificus infection. Therefore, joining with multidisciplinary experts, the Chinese Preventive Medicine Association established a special working group to formulate this consensus, aiming to provide guidance and reference for the diagnosis, treatment and prevention of V. vulnificus infection. Based on existing evidence and the latest research, 6 recommendations were formulated in terms of epidemiology, clinical manifestations, laboratory examination, early diagnosis, clinical evaluation, and infection treatment and prevention.
Humans ; Vibrio Infections/therapy* ; Vibrio vulnificus ; Consensus

Objective To evaluate whether Vibrio vulnificus secreted exotoxin-hemolysin (VVH) can activate platelet, an important blood immune cell, and to explore the possible molecular mechanism of platelet activation by VVH. Methods Transcriptomics and immunohistochemistry were used to analyze whether Vibrio vulnificus infection caused platelet activation in mice. Then, flow cytometry was used to identify whether VVH was the main stimulator of platelet activation. Naturally expressed VVH toxin was purified and prepared. The effects of extracellular and intracellular Ca²⁺ signal inhibitors on VVH activated platelets were evaluated by flow cytometry and Western blotting. The immune activation effect of VVH in the early stage of Vibrio vulnificus infection was analyzed in vivo. Results VVH was the main stimulator of platelet activation in Vibrio vulnificus culture supernatant. Natural VVH can induce the increase of P-selectin (CD62P) on platelet surface, the formation of platelet-neutrophil complex (PNC), and the release of platelet microvesicles. The activation mechanism may be related to the VVH pore-dependent Ca²⁺-calmodulin (CaM) -myosin light chain kinase (MLCK) signaling pathway, which led to the release of platelet alpha particles and cascade activation of platelets. In a mouse model of ALD infected by Vibrio vulnificus gavage, VVH was strongly associated with platelet activation. Conclusion This study shows that VVH is an important platelet activating molecule in the early stage of Vibrio vulnificus infection, and its induction of platelet activation may be related to the pathogenic process.
Animals ; Platelet Activation/drug effects* ; Hemolysin Proteins/pharmacology* ; Vibrio vulnificus/metabolism* ; Mice ; Blood Platelets/drug effects* ; Vibrio Infections/immunology* ; P-Selectin/metabolism* ; Bacterial Proteins ; Female

OBJECTIVE: This study investigated how the natural phytophenol and potent SIRT1 activator resveratrol (RSV) regulate necroptosis during Vibrio vulnificus (V. vulnificus)-induced sepsis and the potential mechanism. METHODS: The effect of RSV on V. vulnificus cytolysin (VVC)-induced necroptosis was analyzed in vitro using CCK-8 and Western blot assays. Enzyme-linked immunosorbent assays and quantitative real-time polymerase chain reaction, western blot, and immunohistochemistry and survival analyses were performed to elucidate the effect and mechanism of RSV on necroptosis in a V. vulnificus-induced sepsis mouse model. RESULTS: RSV relieved necroptosis induced by VVC in RAW264.7 and MLE12 cells. RSV also inhibited the inflammatory response, had a protective effect on histopathological changes, and reduced the expression level of the necroptosis indicator pMLKL in peritoneal macrophages, lung, spleen, and liver tissues of V. vulnificus-induced septic mice in vivo. Pretreatment with RSV downregulated the mRNA of the necroptosis indicator and protein expression in peritoneal macrophages and tissues of V. vulnificus-induced septic mice. RSV also improved the survival of V. vulnificus-induced septic mice. CONCLUSION Our findings collectively demonstrate that RSV prevented V. vulnificus-induced sepsis by attenuating necroptosis, highlighting its potency in the clinical management of V. vulnificus-induced sepsis.
Animals ; Mice ; Necroptosis ; Resveratrol/therapeutic use* ; Vibrio vulnificus ; Sepsis/drug therapy* ; Blotting, Western

This article analyzed the medical records of two patients with Vibrio vulnificus primary sepsis who were admitted to the First Affiliated Hospital of Naval Medical University and reviewed the latest literature. On November 6, 2019, a 54-year-old male patient was admitted to the hospital. The patient's lower limbs were red, swollen, and painful with ecchymosis and hemorrhagic bullae after he ate freshwater products. The emergency fasciotomy was performed 3 h after admission, and the multiple organ failure occurred after operation. The patient was given up treatment 24 h after admission. On August 12, 2020, a 73-year-old male patient was admitted to the hospital. He was in shock state on admission and had hemorrhagic bullae on his right lower limb after he ate seafood. At 3 h post admission, he underwent emergency surgical exploration and amputation of right thigh. Six days later, he received negative pressure wound treatment on the stump. On the 13^th day post admission, his families forgo the active treatment and he died 15 d after admission. The two cases were both failed to be diagnosed at the first time, and the disease progressed rapidly. Necrotizing fasciitis and multiple organ failure occurred. After the diagnosis was confirmed, timely fasciotomy and high amputation were performed respectively. The microbiological examinations both reported Vibrio vulnificus. Although the 2 cases were not cured successfully, the course of disease and some indexes of patient with early amputation were better than those of patients with fasciotomy. Vibrio vulnificus is widely distributed and frequently detected in fresh water products. The pathogenic pathway is fuzzy and complex, and it is easy to be misdiagnosed. It is necessary to establish the treatment process of Vibrio vulnificus sepsis. Early and aggressive surgical intervention should be carried out as soon as possible, fasciotomy and debridement should be thorough, and the patients with hemorrhagic bullae should be amputated early. Postoperative comprehensive measures are also important for improving the survival rate of patients.
Aged ; Fasciitis, Necrotizing/surgery* ; Humans ; Male ; Middle Aged ; Multiple Organ Failure ; Sepsis/diagnosis* ; Vibrio Infections/pathology* ; Vibrio vulnificus

OBJECTIVES: Pathogenic Vibrio species are widely distributed in warm estuarine and coastal environments, and can infect humans through the consumption of raw or mishandled contaminated seafood and seawater. For this reason, the distribution of these bacteria in South Korea was investigated.METHODS: Seawater samples were collected from 145 coastal area points in the aquatic environment in which Vibrio species live. Environmental data (i.e., water temperature, salinity, turbidity, and atmospheric temperature) was collected which may help predict the distribution of the species (data not shown). Seawater samples were filtered, and incubated overnight in alkaline peptone water, at 37°C. Using species-specific polymerase chain reaction methods, screening tests were performed for the hlyA, ctxA, vvhA, and tlh genes. Clones of pathogenic Vibrio species were isolated using 3 selective plating media.RESULTS: In 2017, total seawater isolation rates for Vibrio vulnificus, Vibrio cholerae (non-pathogenic, non-O1, non-O139 serogroups), and Vibrio parahaemolyticus were 15.82%, 13.18%, 65.80%, respectively. However, in 2018 isolation rates for each were 21.81%, 19.40%, and 70.05%, respectively.CONCLUSION: The isolation rates of pathogenic Vibrio species positively correlated with the temperature of seawater and atmosphere, but negatively correlated with salinity and turbidity. From 2017 to 2018, the most frequent seawater-isolated Vibrio species were V. parahaemolyticus (68.10 %), V. vulnificus (16.54%), and non-toxigenic V. cholerae (19.58%). Comprehensive monitoring, prevention, and control efforts are needed to protect the public from pathogenic Vibrio species.
Atmosphere ; Bacteria ; Cholera ; Clone Cells ; Humans ; Korea ; Mass Screening ; Peptones ; Polymerase Chain Reaction ; Salinity ; Seafood ; Seawater ; Vibrio cholerae ; Vibrio parahaemolyticus ; Vibrio vulnificus ; Vibrio ; Water

PURPOSE: The house dust mite (HDM) is one of the most important sources of indoor allergens and a significant cause of allergic rhinitis and allergic asthma. Our previous studies demonstrated that Vibrio vulnificus flagellin B (FlaB) plus allergen as a co-treatment mixture improved lung function and inhibited eosinophilic airway inflammation through the Toll-like receptor 5 signaling pathway in an ovalbumin (OVA)- or HDM-induced mouse asthma model. In the present study, we fused the major mite allergen Derp2 to FlaB and compared the therapeutic effects of the Derp2-FlaB fusion protein with those of a mixture of Derp2 and FlaB in a Derp2-induced mouse asthma model. METHODS: BALB/c mice sensitized with Derp2 + HDM were treated with Derp2, a Derp2 plus FlaB (Derp2 + FlaB) mixture, or the Derp2-FlaB fusion protein 3 times at 1-week intervals. Seven days after the final treatment, the mice were challenged intranasally with Derp2, and airway responses and Derp2-specific immune responses were evaluated. RESULTS: The Derp2-FlaB fusion protein was significantly more efficacious in reducing airway hyperresponsiveness, lung eosinophil infiltration, and Derp2-specific IgE than the Derp2 + FlaB mixture. CONCLUSIONS: The Derp2-FlaB fusion protein showed a strong anti-asthma immunomodulatory capacity, leading to the prevention of airway inflammatory responses in a murine disease model through the inhibition of Th2 responses. These findings suggest that the Derp2-FlaB fusion protein would be a promising vaccine candidate for HDM-mediated allergic asthma therapy.
Allergens ; Animals ; Asthma ; Eosinophils ; Flagellin ; Immunoglobulin E ; Inflammation ; Lung ; Mice ; Mites ; Ovalbumin ; Pyroglyphidae ; Rhinitis, Allergic ; Therapeutic Uses ; Toll-Like Receptor 5 ; Vibrio vulnificus

Porcine epidemic diarrhea (PED) is a highly contagious enteric swine disease. The large economic impact of PED on the swine industry worldwide has made the development of an effective PED vaccine a necessity. S0, a truncated region of the porcine epidemic diarrhea virus (PEDV) spike protein, has been suggested as a candidate antigen for PED subunit vaccines; however, poor solubility problems when the protein is expressed in Escherichia coli, and the inherent problems of subunit vaccines, such as low immunogenicity, remain. Flagellin has been widely used as a fusion partner to enhance the immunogenicity and solubility of many difficult-to-express proteins; however, the conjugation effect of flagellin varies depending on the target antigen or the position of the fusion placement. Here, we conjugated flagellin, Vibrio vulnificus FlaB, to the N- and C-termini of S0 and evaluated the ability of the fusion to enhance the solubility and immunogenicity of S0. Flagellin conjugation in the presence of the trigger factor chaperone tig greatly improved the solubility of the fusion protein (up to 99%) regardless of its conjugation position. Of importance, flagellin conjugated to the N-terminus of S0 significantly enhanced S0-specific humoral immune responses compared to other recombinant antigens in Balb/c mice. The mechanism of this phenomenon was investigated through in vitro and in vivo studies. These findings provide important information for the development of a novel PED vaccine and flagellin-based immunotherapeutics.
Animals ; Diarrhea ; Escherichia coli ; Flagellin ; Immunity, Humoral ; In Vitro Techniques ; Mice ; Porcine epidemic diarrhea virus ; Solubility ; Swine ; Swine Diseases ; Vaccines, Subunit ; Vibrio vulnificus ; Vibrio

Vibrio vulnificus is a gram-negative bacterium that can cause serious, potentially fatal infections. V. vulnificus causes three distinct syndromes: an overwhelming primary septicemia caused by consuming contaminated seafood, wound infections acquired when an open wound is exposed to contaminated warm seawater, and gastrointestinal tract-limited infections. Case-fatality rates are higher than 50% for primary septicemia, and death typically occurs within 72 hours of hospitalization. Risk factors for V. vulnificus infection include chronic liver disease, alcoholism, and hematological disorders. When V. vulnificus infection is suspected, appropriate antibiotic treatment and surgical interventions should be performed immediately. Third-generation cephalosporin with doxycycline, or quinolone with or without third-generation cephalosporin, may be potential treatment options for patients with V. vulnificus infection.
Alcoholism ; Diagnosis ; Doxycycline ; Hospitalization ; Humans ; Liver Diseases ; Prognosis ; Public Health* ; Risk Factors ; Seafood ; Seawater ; Sepsis ; Vibrio vulnificus* ; Vibrio* ; Wound Infection ; Wounds and Injuries

Necrotizing fasciitis caused by Vibrio vulnificus can rapidly progress to septic shock and death. Hence, early surgical debridement of the involved tissue is vital. However, this can be a challenging task due to the coagulopathy and unstable conditions often associated with these patients. Herein, we present a patient with necrotizing fasciitis caused by V. vulnificus who received extracorporeal membrane oxygenation (ECMO) support for refractory hypotension. After initiating ECMO, his vital signs stabilized, and lactate, C-reactive protein, and procalcitonin levels continued to decrease. He underwent several rounds of surgical debridement and vacuum-assisted drainage on both lower legs. On ECMO day 15, he was successfully weaned off the device and his condition was uneventful for several days. However, on the 24th day of intensive care unit (ICU), he was again placed on ECMO due to clinical deterioration. On ICU day 32, he underwent bilateral below-knee amputations due to delayed wound healing. Unfortunately, he subsequently developed multi-organ failure and died. Nonetheless, this case is instructive regarding the potential use of ECMO. We suggest that ECMO could provide the necessary time for sepsis patients to undergo aggressive medical and surgical interventions.
Amputation ; C-Reactive Protein ; Debridement ; Drainage ; Extracorporeal Membrane Oxygenation* ; Fasciitis ; Fasciitis, Necrotizing ; Humans ; Hypotension ; Intensive Care Units ; Lactic Acid ; Leg ; Sepsis* ; Shock, Septic ; Vibrio vulnificus* ; Vibrio* ; Vital Signs ; Wound Healing

PURPOSE: Recombinant subunit vaccines provide safe and targeted protection against microbial infections. However, the protective efficacy of recombinant subunit vaccines tends to be less potent than the whole cell vaccines, especially when they are administered through mucosal routes. We have reported that a bacterial flagellin has strong mucosal adjuvant activity to induce protective immune responses. In this study, we tested whether FlaB could be used as a fusion partner of subunit vaccine for tetanus. MATERIALS AND METHODS: We constructed fusion proteins consisted with tetanus toxin fragment C (TTFC), the nontoxic C-terminal portion of tetanus toxin, and a Toll-like receptor 5 agonist from Vibrio vulnificus (FlaB). Mice were intranasally administered with fusion protein and protective immune responses of the vaccinated mice were analyzed. RESULTS: FlaB-TTFC recombinant protein induced strong tetanus-specific antibody responses in both systemic and mucosal compartments and prolonged the survival of mice after challenge with a supra-lethal dose of tetanus toxin. CONCLUSION: This study establishes FlaB as a successful fusion partner for recombinant subunit tetanus vaccine applicable through mucosal route, and it further endorses our previous observations that FlaB could be a stable adjuvant partner for mucosal vaccines.
Animals ; Antibody Formation ; Flagellin* ; Mice ; Tetanus ; Tetanus Toxin* ; Tetanus Toxoid ; Toll-Like Receptor 5 ; Vaccines ; Vaccines, Subunit ; Vibrio vulnificus