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Frontiers in Immunology 2023is a kind of zoonotic pathogen, which can cause bacterial septicemia in fish and bring huge economic losses to global aquaculture. Outer membrane proteins (Omps) are...
is a kind of zoonotic pathogen, which can cause bacterial septicemia in fish and bring huge economic losses to global aquaculture. Outer membrane proteins (Omps) are conserved antigens of , which can be developed as subunit vaccines. To evaluate the protective efficacy of inactivated vaccine and recombinant outer membrane protein A (OmpA) subunit vaccine against in juvenile , the present study investigated the immunogenicity and protective effects of both vaccines, as well as the non-specific and specific immune response of . Compared with the non-vaccinated group, both inactivated and OmpA subunit vaccines improved the survival rate of upon infection. The protective effects of OmpA vaccine groups were better than that of the inactivated vaccine groups, which should be attributed to the reduced bacterial load and enhanced host immunity in the vaccinated fish. ELISA assay showed that the titer of serum immunoglobulin M (IgM) specific to up-regulated significantly in the OmpA subunit vaccine groups at 14 d post infection (dpi), which should contribute to better immune protective effects. In addition, vaccination enhanced host bactericidal abilities might also attribute to the regulation of the activities of hepatic and serum antimicrobial enzymes. Moreover, the expression of immune-related genes ( and ) increased in all groups post infection, which was more significant in the vaccinated groups. Furthermore, the number of immunopositive cells exhibiting different epitopes (CD8, IgM, IgD and IgZ) that were detected by immunohistochemical assay had increased in the vaccinated groups post infection. These results show that vaccination effectively stimulated host immune response (especially OmpA vaccine groups). In conclusion, these results indicated that both the inactivated vaccine and OmpA subunit vaccine could protect juvenile against infection, of which OmpA subunit vaccine provided more effective immune protection and can be used as an ideal candidate for the vaccine.
Topics: Animals; Aeromonas hydrophila; Vaccines, Inactivated; Bacterial Vaccines; Cypriniformes; Immunoglobulin M; Vaccines, Synthetic; Vaccines, Subunit
PubMed: 36969197
DOI: 10.3389/fimmu.2023.1133742 -
Virulence Dec 2022The molecular mechanisms underlying -pathogenesis are not well understood. Using head kidney macrophages (HKM) of , we previously reported the role of ER-stress in...
The molecular mechanisms underlying -pathogenesis are not well understood. Using head kidney macrophages (HKM) of , we previously reported the role of ER-stress in -induced pathogenesis. Here, we report that PI3K/PLC-induced cytosolic-Ca imbalance induces the expression of pro-apoptotic ER-stress marker, CHOP in infected HKM. CHOP promotes HKM apoptosis by inhibiting AKT activation and enhancing JNK signaling. Elevated mitochondrial ROS (mtROS) was recorded which declined significantly by ameliorating ER-stress and in the presence of ER-Ca release modulators (2-APB and dantrolene) and mitochondrial-Ca uptake inhibitor, Ru360, together suggesting the role of ER-mitochondrial Ca dynamics in mtROS generation. Inhibiting mtROS production reduced HKM death implicating the pro-apoptotic role of mtROS in -pathogenesis. The expression of autophagic proteins (LC3B, beclin-1, and atg 5) was suppressed in the infected HKM. Our results with autophagy-inducer rapamycin demonstrated that impaired autophagy favored the cytosolic accumulation of mitochondrial DNA (mtDNA) and the process depended on mtROS levels. Enhanced caspase-1 activity and IL-1β production was detected and transfection studies coupled with pharmacological inhibitors implicated mtROS/mtDNA axis to be crucial for activating the caspase-1/IL-1β cascade in infected HKM. RNAi studies further suggested the involvement of IL-1β in generating pro-apoptotic NO in -infected HKM. Our study suggests a novel role of ER-mitochondria cross-talk in regulating pathogenesis. Based on our observations, we conclude that induces ER-stress and inhibits mitophagy resulting in mitochondrial dysfunction which leads to mtROS production and translocation of mtDNA into cytosol triggering the activation of caspase-1/IL-1β-mediated NO production, culminating in HKM apoptosis.
Topics: Aeromonas hydrophila; Animals; Apoptosis; Autophagy; Caspase 1; Cytosol; DNA, Mitochondrial; Interleukin-1beta; Macrophages; Mitochondria; Nitric Oxide; Reactive Oxygen Species
PubMed: 34967692
DOI: 10.1080/21505594.2021.2018767 -
The Journal of Veterinary Medical... Dec 2019Aeromonas hydrophila causes disease in fish known as Motile Aeromonas Septicemia (MAS), also named as bacterial hemorrhagic septicemia. In this study, a pathogenic A....
Aeromonas hydrophila causes disease in fish known as Motile Aeromonas Septicemia (MAS), also named as bacterial hemorrhagic septicemia. In this study, a pathogenic A. hydrophila strain was isolated from common carp Cyprinus carpio L., which were suffering from severe hemorrhagic septicemia. According to the phylogenetic analysis derived from 16S rDNA sequence, the isolate formed a single branch in the A. hydrophila group, named AhHN1. Artificial infection results indicated that AhHN1 showed strong pathogenicity in C. carpio and the LD was 1.38 × 10 CFU/fish, the clinical symptoms and pathological features of infected fish were similar to those observed in natural infections. The antimicrobial susceptibility testing revealed that AhHN1 resistance to more than 13 kinds of antimicrobial agents. However, the AhHN1 strain exhibited an extremely sensitivity to enrofloxacin, the in vitro activities of enrofloxacin were subsequently investigated and drug selection window (MSW) was 0.0016-0.0125 µg/ml. Pharmacokinetics data showed that plasma concentration of enrofloxacin was 0.0016, 0.0148 and 0.0282 µg/ml at 24 hr after orally administered with 2.5, 5 and 10 mg/kg enrofloxacin. Moreover, dosing once a day of 2.5, 5 and 10 mg/kg enrofloxacin, which the relative protection ratio (RPS) was amounted to 33.3, 66.7, and 83.3%, respectively. Therefore, 5 mg/kg enrofloxacin was considered to be the rational regimen for controlling AhHN1 infection in C. carpio in the countries where the use of enrofloxacin is permitted in aquaculture. The aim of this study was to establish a scientific medication regimen for the prevention and therapy of the mutidrug-resistant A. hydrophila infection.
Topics: Aeromonas hydrophila; Animals; Anti-Bacterial Agents; Aquaculture; Carps; Drug Resistance, Multiple; Enrofloxacin; Fish Diseases; Gram-Negative Bacterial Infections; Hemorrhagic Septicemia
PubMed: 31406034
DOI: 10.1292/jvms.19-0025 -
Virulence Dec 2021() can cause a number of diseases in both human and animals. related infections in aquaculture cause severe economic losses every year throughout the world. The...
() can cause a number of diseases in both human and animals. related infections in aquaculture cause severe economic losses every year throughout the world. The emergence of antibiotic resistance that is due to the abuse of antibiotics has limited the application of antibiotics. Thus, novel approaches are needed to combat with treatment failure of antibiotics caused by resistant bacterial strains. Aerolysin plays a critical role in the pathogenesis of and has been considered as a novel target for developing drugs based on anti-virulence strategies. Here, we reported that luteolin, a natural product with no anti- activity, could reduce aerolysin-induced hemolysis by inhibiting aerolysin activity. The binding mode was simulated by molecular docking and dynamics simulation. Then the main binding sites were confirmed by fluorescence quenching assays. We found that luteolin could hindered the formation of functional heptamer of aerolysin according to the results of the oligomerization assay. Moreover, luteolin could protect A549 cells from aerolysin mediated cell death and increase the survival rate of -infected channel catfish. These findings suggest a novel approach to developing drugs fighting against , and luteolin can be a promising drug candidate for treatment of -associated infections.
Topics: A549 Cells; Aeromonas hydrophila; Animals; Bacterial Toxins; Biological Products; Carps; Fish Diseases; Humans; Luteolin; Molecular Docking Simulation; Pore Forming Cytotoxic Proteins; Virulence
PubMed: 33372840
DOI: 10.1080/21505594.2020.1867455 -
Frontiers in Cellular and Infection... 2022In this paper, the whole genome of the multidrug-resistant MX16A was comprehensively analyzed and compared after sequencing by PacBio RS II. To shed light on the drug...
In this paper, the whole genome of the multidrug-resistant MX16A was comprehensively analyzed and compared after sequencing by PacBio RS II. To shed light on the drug resistance mechanism of MX16A, a Kirby-Bauer disk diffusion method was used to assess the phenotypic drug susceptibility. Importantly, resistance against β-lactam, sulfonamides, rifamycins, macrolides, tetracyclines and chloramphenicols was largely consistent with the prediction analysis results of drug resistance genes in the CARD database. The varied types of resistance genes identified from MX16A revealed multiple resistance mechanisms, including enzyme inactivation, gene mutation and active effusion. The publicly available complete genomes of 35 strains on NCBI, including MX16A, were downloaded for genomic comparison and analysis. The analysis of 33 genomes with ANI greater than 95% showed that the pan-genome consisted of 9556 genes, and the core genes converged to 3485 genes. In summary, the obtained results showed that exhibited a great genomic diversity as well as diverse metabolic function and it is believed that frequent exchanges between strains lead to the horizontal transfer of drug resistance genes.
Topics: Aeromonas hydrophila; Anti-Bacterial Agents; Drug Resistance, Microbial; beta-Lactams; Genomics
PubMed: 36405966
DOI: 10.3389/fcimb.2022.1042350 -
Virulence Dec 2022The immunogenicity of Aha1, an OMP of mediating the adhesion of bacteria onto the mucosal surface of hosts has been established. In this study, recombinant vectors,...
The immunogenicity of Aha1, an OMP of mediating the adhesion of bacteria onto the mucosal surface of hosts has been established. In this study, recombinant vectors, pPG1 and pPG2, carrying a 1366 bp DNA fragment that was responsible for encoding the 49 kDa Aha1 from were constructed, respectively, then electroporated into a probiotic strain CC16 separately to generate two types of recombinants, pPG1-Aha1 (Lc-pPG1-Aha1) and -pPG2-Aha1 (Lc-pPG2-Aha1). Subsequently, these were orally administered into common carps to examine their immunogenicity. The expression and localization of the expressed Aha1 protein relative to the carrier was validated via Western blotting, flow cytometry, and immune fluorescence separately. The recombinant vaccines produced were shown high efficacies, stimulated higher level of antibodies and AKP, ACP, SOD, LZM, C3, C4 in serum in hosts. Immune-related gene expressions of cytokines including IL-10, IL-1β, TNF-α, IFN-γ in the livers, spleens, HK, and intestines were up-regulated significantly. Besides, a more potent phagocytosis response was observed in immunized fish, and higher survival rates were presented in immunized with Lc-pPG1-Aha1 (60%) and Lc-pPG2-Aha1 (50%) after re-infection with virulent strain . Moreover, the recombinant were shown a stronger propensity for survivability in the intestine in immunized fish. Taken together, the recombinant strains might be promising candidates for oral vaccination against infections in common carps.
Topics: Aeromonas hydrophila; Animals; Bacterial Vaccines; Carps; Lacticaseibacillus casei; Vaccination
PubMed: 35499101
DOI: 10.1080/21505594.2022.2063484 -
Frontiers in Cellular and Infection... 2023is an important pathogen that mainly harms aquatic animals and exhibits resistance to a variety of antibiotics. This study investigated the effect of...
BACKGROUND
is an important pathogen that mainly harms aquatic animals and exhibits resistance to a variety of antibiotics. This study investigated the effect of epigallocatechin-3-gallate (EGCG) on the virulence factors of and its impact on adhesion, invasion, and cytotoxicity in Caco-2 cells. The potential mechanism of antibacterial activity of EGCG was investigated by transcriptomic analysis.
RESULTS
EGCG not only inhibited the production of biofilm, hemolytic activity, motility, and protease activity of , but also reduced its adhesion, invasion, and cytotoxicity in Caco-2 cells. Transcriptomic analysis indicated that the antimicrobial activity of EGCG may be achieved by weakening the chemotaxis and stress response of the bacteria, as well as inhibiting the TonB system. Animal studies demonstrated that EGCG can significantly improve the survival rate and organs damage of zebrafish infected with .
CONCLUSION
EGCG would be a potential alternative drug for the prevention and treatment of infections by anti-virulence mechanism.
Topics: Animals; Humans; Aeromonas hydrophila; Zebrafish; Caco-2 Cells; Transcriptome; Anti-Bacterial Agents; Gram-Negative Bacterial Infections
PubMed: 37868352
DOI: 10.3389/fcimb.2023.1271448 -
Brazilian Journal of Microbiology :... Mar 2020To develop an alternative bio-control measure for multi-drug resistant pathogenic Aeromonas hydrophila, which causes motile Aeromonas septicemia in fish, novel virulent...
To develop an alternative bio-control measure for multi-drug resistant pathogenic Aeromonas hydrophila, which causes motile Aeromonas septicemia in fish, novel virulent phage (AHP-1) was isolated from carp tissues. Morphological analysis by transmission electron microscopy revealed that AHP-1 belongs to Myoviridae family. AHP-1 displayed 81% of moderate adsorption by 25 min, and latent period of 40 min with burst size of 97 PFU mL at an optimal multiplicity of infection (MOI) 0.1. AHP-1 was stable over a broad range of pH (4-11), temperature (4-50 °C), and salinity (0.1-3.5%). Both time and MOI dependent in vitro A. hydrophila growth inhibition was observed with AHP-1. AHP-1 (10 MOI) showed higher growth inhibition against A. hydrophila than chloramphenicol (5 μg mL), and combined treatment was more promising than individuals. Immune gene expression analysis of zebrafish upon continuous bath exposure to AHP-1 resulted significantly higher (il-6 and sod-1) or slight induction (tnf-α, il1-β, il-10, and cxcl-8a) than controls at beginning of the phage exposure, but those lowered to basal level by day 12 post-phage exposure. It suggests no adverse immune responses have occurred for the AHP-1 dose that used, and have potential for the phage therapy. Further detailed in vivo studies are needed to confirm the protective efficacy of newly isolated AHP-1 against A. hydrophila infection.
Topics: Aeromonas hydrophila; Animals; Bacteriophages; Biological Control Agents; Carps; Chloramphenicol; Fish Diseases; Fishes; Immunity, Cellular; Myoviridae; Zebrafish
PubMed: 31691176
DOI: 10.1007/s42770-019-00178-z -
Le Infezioni in Medicina Dec 2019Aeromonas hydrophila (A. hydrophila) occasionally causes necrotizing fasciitis (NF) and sepsis in immunocompromised hosts. NF is associated with high mortality. In cases...
Aeromonas hydrophila (A. hydrophila) occasionally causes necrotizing fasciitis (NF) and sepsis in immunocompromised hosts. NF is associated with high mortality. In cases of septic shock due to A. hydrophila, mortality is nearly 100%. Our 47-year-old male patient was diagnosed with NF and septic shock due to A. hydrophila. He had not been exposed to fresh or slightly salty water, which is where the bacterium is typically found, so its origin in this case is unclear. This is the first known case in which the patient was able to be completely cured without amputation. NF was suspected from his sepsis, medical history including alcoholic cirrhosis, and a severely poor general condition, but his skin lesions were mild. We promptly made an exploratory incision and debrided his legs. NF could then be diagnosed. At an early stage, A. hydrophila was recognized as a possible pathogen of NF because of the patient's medical background and the Gram stain findings of intraoperative exudate. Minocycline in addition to carbapenem and vancomycin plus clindamycin were administered as empiric therapy. When A. hydrophila was detected in the blood culture, ciprofloxacin was administered as definitive therapy. Successful treatment of NF requires early diagnosis, prompt debridement from onset and adequate empirical antibiotic therapy.
Topics: Aeromonas hydrophila; Fasciitis, Necrotizing; Gram-Negative Bacterial Infections; Humans; Male; Middle Aged; Remission Induction; Sepsis
PubMed: 31846994
DOI: No ID Found -
Microbiological Research Sep 2021Bacillus amyloliquefaciens X030 (BaX030) has broad-spectrum antibacterial activity against the fish pathogens Aeromonas hydrophila and Aeromonas veronii. To improve its...
Bacillus amyloliquefaciens X030 (BaX030) has broad-spectrum antibacterial activity against the fish pathogens Aeromonas hydrophila and Aeromonas veronii. To improve its antibacterial effect, BaX030 was subjected to compound mutagenesis of atmospheric and room temperature plasma (ARTP) and nitrosoguanidine (NTG). The results showed that, compared with the original strain, the production of macrolactin A and oxydifficidin in mutated strain N-11 increased to 39 % and 268 %, respectively. The re-sequencing analysis suggested that there were SNPs and InDels in the gene clusters focused on the sucrose utilization pathway, glycolysis pathway and fatty acid synthesis pathway. Scanning electron microscopy revealed that strain N-11 became thin and long. The qRT-PCR results indicated that the expression of immune factors in the liver or kidney tissue of grass carp increased after feeding with N-11. H&E staining and protection experiments also showed that the mortality and surface symptoms of grass carp infected by the two pathogens were significantly reduced. The study identified a probiotic strain with potential application value in aquaculture production and provided a new strategy for the discovery of new strains with higher antibacterial biological activity.
Topics: Aeromonas hydrophila; Aeromonas veronii; Animals; Bacillus amyloliquefaciens; Carps; Fish Diseases; Microbial Interactions; Mutation; Probiotics
PubMed: 34139525
DOI: 10.1016/j.micres.2021.126801