A cocktail of three virulent bacteriophages prevents Vibrio cholerae infection in animal models

Yen, Minmin; Cairns, Lynne S.; Camilli, Andrew

doi:10.1038/ncomms14187

Cited by 199 publications

(153 citation statements)

References 23 publications

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“…But earlier studies showed the use of cocktail of phages to eliminate the bacterial infection [21, 22]. This study shows that the effectiveness of phage therapy depends only of the ability of single phage to reduce the bacterial load and not on the complexity of phage preparations.…”

Section: Discussionmentioning

confidence: 77%

The therapeutic potential of bacteriophages targeting gram-negative bacteria using Galleria mellonella infection model

2018

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BackgroundPhage therapy is the therapeutic use of bacteriophages to treat highly drug resistant bacterial infections. The current surge in bacteriophage therapy is motivated mainly because of the emergence of antibiotic-resistant bacteria in clinics. This study evaluated the therapeutic potential of three bacteriophages isolated against Escherichia coli ec311, Klebsiella pneumoniae kp235 and Enterobacter cloacae el140 strains using Galleria mellonella. The in vitro activity of three different phages belonging to Podoviridae and Myoviridae families was studied by the double agar overlay method against multi-drug resistant strains. Larval survivability studies were performed to evaluate the potential of phages against infection using G. mellonella.ResultsAll the three phages were found to have potential to infect the host bacterial strains. For in vivo studies it was observed that E. coli and E. cloacae infected larvae, should be treated with three phage doses (20 μL, 104 PFU/mL) at 6 h interval to achieve 100% survival rate. But in the case of K. pneumoniae, a single phage dose treatment showed promising outcome. When mixed bacterial infections (all three bacterial cultures at 108 CFU/mL) were tested, minimum of four doses of phage cocktail (three phages) at 6 h interval was necessary to recover the larvae. All the results were confirmed by enumerating bacteria from the larvae.ConclusionOur data shows that although in vitro studies showed high infectivity of phages, for in vivo models multiple phage doses were required for effective treatment.Electronic supplementary materialThe online version of this article (10.1186/s12866-018-1234-4) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 77%

The therapeutic potential of bacteriophages targeting gram-negative bacteria using Galleria mellonella infection model

2018

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“…The encapsulated dose was ~ 2 x 10 8 PFU g -1 of phage microparticles. One gram of microparticles would therefore deliver a ~10 7 PFU dose which is similar to therapeutic doses given in a number of animal studies [28], [85–89]. Nale et al [28] in their hamster C .…”

Section: Discussionmentioning

confidence: 81%

Microencapsulation of Clostridium difficile specific bacteriophages using microfluidic glass capillary devices for colon delivery using pH triggered release

et al. 2017

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The prevalence of pathogenic bacteria acquiring multidrug antibiotic resistance is a global health threat to mankind. This has motivated a renewed interest in developing alternatives to conventional antibiotics including bacteriophages (viruses) as therapeutic agents. The bacterium Clostridium difficile causes colon infection and is particularly difficult to treat with existing antibiotics; phage therapy may offer a viable alternative. The punitive environment within the gastrointestinal tract can inactivate orally delivered phages. C. difficile specific bacteriophage, myovirus CDKM9 was encapsulated in a pH responsive polymer (Eudragit® S100 with and without alginate) using a flow focussing glass microcapillary device. Highly monodispersed core-shell microparticles containing phages trapped within the particle core were produced by in situ polymer curing using 4-aminobenzoic acid dissolved in the oil phase. The size of the generated microparticles could be precisely controlled in the range 80 μm to 160 μm through design of the microfluidic device geometry and by varying flow rates of the dispersed and continuous phase. In contrast to free ‘naked’ phages, those encapsulated within the microparticles could withstand a 3 h exposure to simulated gastric fluid at pH 2 and then underwent a subsequent pH triggered burst release at pH 7. The significance of our research is in demonstrating that C. difficile specific phage can be formulated and encapsulated in highly uniform pH responsive microparticles using a microfluidic system. The microparticles were shown to afford significant protection to the encapsulated phage upon prolonged exposure to an acid solution mimicking the human stomach environment. Phage encapsulation and subsequent release kinetics revealed that the microparticles prepared using Eudragit® S100 formulations possess pH responsive characteristics with phage release triggered in an intestinal pH range suitable for therapeutic purposes. The results reported here provide proof-of-concept data supporting the suitability of our approach for colon targeted delivery of phages for therapeutic purposes.

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“…; Yen et al . ). However, in order to further develop phages as antimicrobial agents, it is necessary to investigate the impact of more complex formulations which include additional active and excipient components (Abedon ).…”

Section: Resultsmentioning

confidence: 97%

In vitroactivity of a combination of bacteriophages and antimicrobial plant extracts

Pimchan

Cooper

Eumkeb

et al. 2018

Lett Appl Microbiol

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Significance and Impact of Study: This preliminary study provides insights into the potential combination of bacteriophages and antimicrobial plant bulk extracts to target bacterial pathogens. It is to our knowledge the first time in which virulent bacteriophages have been combined with antimicrobial plant extracts. AbstractThe continuing threat of antimicrobial resistance presents a considerable challenge to researchers to develop novel strategies ensuring that bacterial infections remain treatable. Many plant extracts have been shown to have antibacterial properties and could potentially be combined with other antibacterial agents to create more effective formulations. In this study, the antibacterial activity of three plant extracts and virulent bacteriophages have been assessed as individual components and in combination. When assessed with a modified suspension test, these plant extracts also exhibit antiviral activity at bacterial inhibitory concentrations. Hence, to investigate any potential additive effects between the extracts and virulent phages, the extracts were tested at subantiviral concentrations. Phages alone and in combination with plant extracts significantly reduced (P < 0Á05) the bacterial concentration compared to untreated and extract treated controls up to 6 h (2-3log 10 ), but this reduction did not extend to 24 h. In most cases, the phage and extract combinations did not significantly reduce bacterial content compared to phages alone. Additionally, there was little impact on the ability of the phages to reproduce within their bacterial hosts. To our knowledge, this study represents the first of its kind, in which antimicrobial plant extracts have been combined with virulent phages and has highlighted the necessity for plant extracts to be functionally characterized prior to the design of combinatorial therapies.

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A cocktail of three virulent bacteriophages prevents Vibrio cholerae infection in animal models

Cited by 199 publications

References 23 publications

The therapeutic potential of bacteriophages targeting gram-negative bacteria using Galleria mellonella infection model

The therapeutic potential of bacteriophages targeting gram-negative bacteria using Galleria mellonella infection model

Microencapsulation of Clostridium difficile specific bacteriophages using microfluidic glass capillary devices for colon delivery using pH triggered release

In vitroactivity of a combination of bacteriophages and antimicrobial plant extracts

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