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Aeromonas hydrophila ( A. hydrophila ) can cause a number of diseases in both human and animals. A. hydrophila- 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 A. hydrophila 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- A. hydrophila 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 A. hydrophila -infected channel catfish. These findings suggest a novel approach to developing drugs fighting against A. hydrophila , and luteolin can be a promising drug candidate for treatment of A. hydrophila -associated infections.

The use of bdellovibrios has been regarded as an alternative to control multidrug-resistant pathogens and fish bacteriosis. However, scarce information is available on the potential of bdellovibrios in the presence of copper sulfate, which is an algicide widely used to treat cyanobacterial blooms in aquaculture. In the present study, the effects of copper sulfate at sublethal and lethal levels (0.1 and 1.0 mg·L -1 ) on Bdellovibrio sp. strain BDF-H16 were evaluated. The growth of Bdellovibrio sp. strain BDF-H16 was significantly promoted by both concentrations of copper sulfate, but less so by the lethal concentration. The bacteriolysis of gibel carp-pathogenic Aeromonas hydrophila by Bdellovibrio sp. strain BDF-H16 was also stimulated by copper sulfate in both solid and liquid media. However, Bdellovibrio sp. strain BDF-H16 with 0.1 mg·L -1 copper sulfate clearly inhibited infection of gibel carps by A. hydrophila better than Bdellovibrio sp. strain BDF-H16 with 1.0 mg·L -1 copper sulfate did.

Aeromonas hydrophila is a common zoonotic pathogen which can cause several infections both in human and animals, particular aquatic animals. Antibiotics have been widely used in the treatment of A. hydrophila infections, however, the development of resistance has limited the treatment for these infections. There is an urgent need for novel agents and strategies against these infections. Aerolysin, a pore-forming toxin secreted by most pathogenic A. hydrophila, is known to contribute to the pathogenesis of A. hydrophila infections. Therefore, aerolysin has been identified as a potential target for drug discovery. In this paper, we found that magnolol, a natural compound without anti -A. hydrophila activity, could significantly inhibit the hemolytic activity of A. hydrophila culture supernatants by inhibiting the transcription of the aerolysin encoding gene aerA at low concentrations. Furthermore, the survival assay showed that magnolol could significantly reduce the mortality induced by A. hydrophila infection in channel catfish (Ictalurus punctatus). Taken together, these findings provide a potent agent against A. hydrophila infections., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Aeromonas hydrophila is an opportunistic pathogen that can cause a number of infectious diseases in fish and is widely distributed in aquatic environments. Antibiotics are the main approach against A. hydrophila infections, while the emergence of resistant bacteria limits the application of antibiotics. Here, quorum-sensing (QS) was defined as the target and the inhibitory effects of neem oil against QS of A. hydrophila was studied. The results showed that neem oil could dose-dependently reduce aerolysin, protease, lipase, acyl-homoserine lactones (AHLs), biofilm and swarming motility at sub-inhibitory concentrations. Results of real-time PCR demonstrated that neem oil could down-regulate the transcription of aerA, ahyI and ahyR. Moreover, neem oil showed significant protections to A549 cells and a fish infection model. Taken together, these results indicated that neem oil could be chosen as a promising candidate for the treatment of A. hydrophila infections. [ABSTRACT FROM AUTHOR]

Antibiotics were the main fishery drugs for treating Aeromonas hydrophila (A. hydrophila) infection, which would generate selective pressure and result in the appearance of antibiotic-resistant bacteria. The bacterial quorum sensing (QS) system provides a new alternative strategy against A. hydrophila infection. QS inhibitors can reduce bacterial virulence behaviors by disrupting QS, which has no effect on bacterial growth. Therefore, we studied the effect of cinnamaldehyde from a natural plant extract on the QS of A. hydrophila aiming to reduce its pathogenicity. The efficacy of cinnamaldehyde against A. hydrophila was evaluated from various aspects, including the effects on aerolysin, lipase, protease, swarming motility, biofilm formation, acyl-homoserine lactones (AHLs), and QS-related genes. Moreover, the therapeutic effect of cinnamaldehyde in vitro and in vivo was studied. The results showed that cinnamaldehyde could decrease the virulence phenotypes of A. hydrophila regulated by QS. Moreover, the transcriptions of related genes (aerA, ahyR, and ahyI) were downregulated following the addition of cinnamaldehyde. The in vitro and in vivo therapeutic assays show that cinnamaldehyde could reduce the aerolysin-mediated A549 cell injury and increase the survival rate of crucian carp infected with A. hydrophila. These results indicate that cinnamaldehyde would be a candidate QS inhibitor against A. hydrophila infection. [ABSTRACT FROM AUTHOR]

Aeromonas hydrophila, an opportunistic aquatic pathogen widely spread in aquatic environments, is responsible for a number of infectious diseases in freshwater aquaculture. In addition, A. hydrophila can transmit from diseased fish to humans and results in health problems. The occurrence of antibiotic-resistant bacterial strains restricts the application of antibiotics and is responsible for failure of the treatment. Moreover, residues of antibiotics in aquatic products often threaten the quality and safety. Therefore, alternative strategies are called to deal with infections caused by antibiotic-resistant bacteria. Aerolysin, one of the most important virulence factors of A. hydrophila, is adopted as a unique anti-virulence target on the basis of the anti-virulence strategy to battling infections caused by A. hydrophila. Palmatine, an isoquinoline alkaloid from a variety of herbal medicines that showed no anti-A. hydrophila activity, could reduce hemolysis of the bacterium by decreasing aerolysin production. The results of the qPCR assay demonstrated that the transcription of the aerA gene was suppressed. Moreover, cell viability and in vivo study showed that palmatine treatment could decrease the pathogenicity of A. hydrophila both in vitro and in vivo. In summary, palmatine is a leading compound against A. hydrophila-associated infection in aquaculture by inhibiting the expression of aerolysin. [ABSTRACT FROM AUTHOR]

Aeromonas hydrophila is a pathogenic bacterium that can cause serious infections both in humans and aquatic animals. Antibiotics are the main approach for fighting against the pathogen. However, the emergence of antibiotic resistance has resulted in treatment failure. Therefore, drugs with novel strategies need to be developed. Quorum sensing has been recognized as a promising method for identifying anti-virulence drugs against bacterial infections. The aim of this study was to identify novel drugs targeting quorum sensing of A. hydrophila as alternatives of antibiotics in aquaculture. Thus, hemolytic activity, biofilm formation, qPCR and experimental therapeutics assays were conducted. The results showed that sanguinarine inhibited the growth of A. hydrophila at concentrations higher than 16 μg/mL, but the production of aerolysin and biofilm formation was significantly inhibited at sub-inhibitory concentrations by disrupting the quorum sensing system. Cell viability results showed that sanguinarine could provide protection for A549 cells from aerolysin-induced cell injury. In addition, the mortality of channel catfish administered with sanguinarine at a dosage of 20 mg/kg decreased to 40%, which showed a significant decrease compared with fish in positive group. Taken together, these findings demonstrated that anti-virulence strategies can be a powerful weapon for fighting against bacterial pathogens and sanguinarine appears to be a promising candidate in the treatment of A. hydrophila infections. [ABSTRACT FROM AUTHOR]

Aeromonas hydrophila is an opportunistic pathogen that is responsible for a variety of infectious diseases both in human and animals, particularly aquatic animals. Moreover, the pathogen has become a foodborne pathogen by transmitting from seafood to human. The abuse of antibiotics in aquaculture results in the emergence of antibiotic resistance and treatment failure. Therefore, novel approaches are urgently needed for managing resistant A. hydrophila associated infections. Aerolysin, an essential virulence factor of pathogenic A. hydrophila strain, has been identified as target developing novel drugs against pathogenesis of A. hydrophila. In the present study, genistein, without anti- A. hydrophila activity, was identified that could decrease the production of aerolysin and biofilm formation at a dose-dependent manner. Transcription of aerolysin encoding gene aerA and quorum sensing related genes ahyI and ahyR was significantly down-regulated when co-cultured with genistein. Cell viability studies demonstrated that genistein could significantly improve aerolysin mediated A549 cell injury. Furthermore, genistein could provide a remarkable protection to channel catfish infected with A. hydrophila. These findings indicate that targeting quorum sensing and virulence can be a useful approach developing drugs against A. hydrophila infections in aquaculture. Moreover, genistein can be chosen as a promising candidate in developing drugs against A. hydrophila. [ABSTRACT FROM AUTHOR]

Aeromonas hydrophila (A. hydrophila) is an opportunistic bacterial pathogen widely distributed in the environments, particular aquatic environment. The pathogen can cause a range of infections in both human and animals including fishes. However, the application of antibiotics in treatment of A. hydrophila infections leads to the emergence of resistant strains. Consequently, new approaches need to be developed in fighting this pathogen. Aerolysin, the chief virulence factor produced by pathogenic A. hydrophila strains has been employed as target identifying new drugs. In our present study, we found that morin, a flavonoid without anti-bacterial activity isolated from traditional Chinese medicine, could directly inhibit the hemolytic activity of aerolysin. To determine the binding sites and the action of mechanism of morin against AerA, several assays were performed. Ser36, Pro347, and Arg356 were identified as the main binding sites affecting the conformation of AerA and resulted in block of the heptameric formation. Moreover, morin could protect Vero cells from cell injury mediated by aerolysin. In vivo study showed that morin could provide a protection to channel catfish against A. hydrophila infection. These results demonstrated that morin could be developed as a promising candidate for the treatment of A. hydrophila infections by decreasing the pathogenesis of A. hydrophila. [ABSTRACT FROM AUTHOR]

Aeromonas hydrophila is a major pathogen in aquaculture in China; it is also an emerging pathogen in humans and animals. In recent years, several severe diseases, such as gastroenteritis, meningitis, and skin and soft tissue infections, have been found to be caused by A. hydrophila. Aerolysin and hemolysin are the most important virulence factors secreted by A. hydrophila. Therefore, new drugs targeted at these two toxins can be found in the therapy for A. hydrophila infections, reducing the usage of antibiotics. In this paper, we expressed and purified the aerolysin and hemolysin using a prokaryotic expression system. We found that aerolysin was more toxic than hemolysin, both in vitro and in vivo. The lethal dose ( LD50) of aerolysin and hemolysin was 0.4 and 2.3 µg per fish, respectively. [ABSTRACT FROM AUTHOR]

Aeromonas hydrophila is an opportunistic pathogen responsible for a number of diseases in freshwater farming. Moreover, the bacterium has been identified as a zoonotic pathogen that threatens human health. Antibiotics are widely used for treatments of infectious diseases in aquaculture. However, the abuse of antibiotics has led to the emergence of antimicrobial resistant strains. Thus, novel strategies are required against resistant A. hydrophila strains. The quorum sensing (QS) system, involved in virulence factor production and biofilm formation, is a promising target in identifying novel drugs against A. hydrophila infections. In this study, we found that thymol, at sub-inhibitory concentrations, could significantly reduce the production of aerolysin and biofilm formation by inhibiting the transcription of genes aerA, ahyI, and ahyR. These results indicate that thymol inhibits the quorum sensing system. The protective effects of thymol against A. hydrophila mediated cell injury were determined by live/dead assay and lactate dehydrogenase (LDH) release assay. Moreover, the in vivo study showed that thymol could significantly decrease the mortality of channel catfish infected with A. hydrophila. Taken together, these findings demonstrate that thymol could be chosen as a phytotherapeutic candidate for inhibiting quorum sensing system-mediated aerolysin production and biofilm formation in A. hydrophila. [ABSTRACT FROM AUTHOR]

The overuse of antibiotics in aquaculture brings a range of problems. Therefore, novel approaches alternating antibiotics are urgently needed. Strategies targeting bacterial virulence have become one of the routes developing drugs against bacterial infections. Here, we found that pterostilbene (PSE) could inhibit the activity of aerolysin (AerA) and disrupt quorum sensing (QS) at sub-inhibitory concentrations. Molecular docking and dynamics simulation assays were performed to predict the binding mode and binding sites of AerA-PSE complex. Then we confirmed that PSE bound to the sites of Val189 and Ile302 and prevented AerA forming heptamer with transmembrane pores. In addition, PSE could protect to A549 cells and the channel catfish (Ictalurus punctatus) against AerA mediated cell injury and mortality infected with A. hydrophila. The findings demonstrated that targeting bacterial virulence could be a promising measure identifying agents against A. hydrophila infections. • Pterostilbene is an inhibitor of both aerolysin and quorum sensing of Aeromonas hydrophila. • Pterostilbene could reduce the pathogenicity of Aeromonas hydrophila at sub-inhibitory concentrations. • The main binding sites and mechanism of at pterostilbene against aerolysin was confirmed. [ABSTRACT FROM AUTHOR]

Aeromonas hydrophila is widely distributed in freshwater environments and aquatic products which can cause a variety of infectious diseases to aquatic, terrestrial species and human. However, the emergence of antibiotic resistant strains results in the treatment failure of antibiotics. Therefore, novel strategies need to be clarified. The pathogenesis of the bacterium is composed by the virulence factors, such as hemolytic toxins, biofilm and adhesions. Therefore, aerolysin and biofilm have been developed as targets identifying novel drugs against A. hydrophila infections. In the present study, resveratrol with little anti- A. hydrophila activity could decrease the pathogenesis of A. hydrophila by inhibiting the expression of aerolysin and biofilm formation at sub-inhibitory concentrations. Results of western-blot and qPCR assays demonstrated that RSV could decrease aerolysin and biofilm production by inhibiting aerolysin encoding gene and quorum sensing system. Furthermore, results of cell viability and experimental therapeutics assays indicated that RSV could provide a significant protection both in vitro and in vivo. Taken together, these findings provide a new approach in identifying drugs based on anti-virulence strategies. RSV is a promising candidate anti- A. hydrophila infections by decreasing the production of aerolysin and biofilm. • Resveratrol can decrease the hemolytic activity and biofilm formation by habiting the quorum sensing system. • Resveratrol can provide a significant protection to channel catfish challenged with A. hydrophila. • Findings in the present study offer a novel approach identifying drugs against Aeromonas hydrophila infections. [ABSTRACT FROM AUTHOR]