Phage Therapy in the Era of Synthetic Biology

Barbu, E. Magda; Cady, Kyle C.; Hubby, Bolyn

doi:10.1101/cshperspect.a023879

Cited by 55 publications

(62 citation statements)

References 114 publications

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“…However, the intensive use of antibiotics in treating furunculosis has driven the attendant development of multidrug-resistance in A . salmonicida ( Cabello, 2006 ; Defoirdt et al, 2007 ; Reith et al, 2008 ; Kim et al, 2011 ; Austin and Austin, 2016 ) and has now become a global concern ( Tanji et al, 2005 ; Barbu et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

In Vitro Design and Evaluation of Phage Cocktails Against Aeromonas salmonicida

et al. 2018

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As an alternative approach against multidrug-resistant bacterial infections, phages are now being increasingly investigated as effective therapeutic agents. Here, aiming to design an efficient phage cocktail against Aeromonas salmonicida infections, we isolated and characterized five lytic A. salmonicida phages, AS-szw, AS-yj, AS-zj, AS-sw, and AS-gz. The results of morphological and genomic analysis suggested that all these phages are affiliated to the T4virus genus of the Caudovirales order. Their heterogeneous lytic capacities against A. salmonicida strains were demonstrated by experiments. A series of phage cocktails were prepared and investigated in vitro. We observed that the cocktail combining AS-gz and AS-yj showed significantly higher antimicrobial activity than other cocktails and individual phages. Given the divergent genomes between the phages AS-yj and AS-gz, our results highlight that the heterogeneous mechanisms that phages use to infect their hosts likely lead to phage synergy in killing the host. Conclusively, our study described a strategy to develop an effective and promising phage cocktail as a therapeutic agent to combat A. salmonicida infections, and thereby to control the outbreak of relevant fish diseases. Our study suggests that in vitro investigations into phages are prerequisite to obtain satisfying phage cocktails prior to application in practice.

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Section: Introductionmentioning

confidence: 99%

In Vitro Design and Evaluation of Phage Cocktails Against Aeromonas salmonicida

et al. 2018

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“…P. aeruginosa is an opportunistic pathogen that infects burn wound patients and those with cystic fibrosis (Chatterjee et al, 2016), and is a public health concern due to high rates of multi-drug resistance. Phage therapy is a promising alternative to treating P. aeruginosa infections (Citorik et al, 2014; Barbu et al, 2016; Gorski et al, 2016); therefore, a solid understanding of the molecular phage–host interactions will be essential for the regulation and legislation of phage therapy in the near future (Ceyssens and Lavigne, 2010). In addition, cellular processes targeted by phage, such as essential replication or transcription functions, may point to potential antimicrobial drug targets (Liu et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Transcriptomic and Metabolomics Profiling of Phage–Host Interactions between Phage PaP1 and Pseudomonas aeruginosa

et al. 2017

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The basic biology of bacteriophage–host interactions has attracted increasing attention due to a renewed interest in the therapeutic potential of bacteriophages. In addition, knowledge of the host pathways inhibited by phage may provide clues to novel drug targets. However, the effect of phage on bacterial gene expression and metabolism is still poorly understood. In this study, we tracked phage–host interactions by combining transcriptomic and metabolomic analyses in Pseudomonas aeruginosa infected with a lytic bacteriophage, PaP1. Compared with the uninfected host, 7.1% (399/5655) of the genes of the phage-infected host were differentially expressed genes (DEGs); of those, 354 DEGs were downregulated at the late infection phase. Many of the downregulated DEGs were found in amino acid and energy metabolism pathways. Using metabolomics approach, we then analyzed the changes in metabolite levels in the PaP1-infected host compared to un-infected controls. Thymidine was significantly increased in the host after PaP1 infection, results that were further supported by increased expression of a PaP1-encoded thymidylate synthase gene. Furthermore, the intracellular betaine concentration was drastically reduced, whereas choline increased, presumably due to downregulation of the choline–glycine betaine pathway. Interestingly, the choline–glycine betaine pathway is a potential antimicrobial target; previous studies have shown that betB inhibition results in the depletion of betaine and the accumulation of betaine aldehyde, the combination of which is toxic to P. aeruginosa. These results present a detailed description of an example of phage-directed metabolism in P. aeruginosa. Both phage-encoded auxiliary metabolic genes and phage-directed host gene expression may contribute to the metabolic changes observed in the host.

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“…However, genetic alterations in phage genome by deletion of genes encoding immunogenic peptides can be a response . Such designs can also be used to expand phage host range to use minimal phages for a large number of bacterial infections and to introduce immune evasion properties in phages . But an extensive research in molecular characterization of phage genome using new approaches and new tools is required to use phage potential in therapeutics.…”

Section: Why Phage Therapy?mentioning

confidence: 99%

The dawn of phage therapy

Rehman

Ali

Khan

et al. 2019

Reviews in Medical Virology

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Bacteriophages or phages, being the most abundant entities on earth, represent a potential solution to a diverse range of problems. Phages are successful antibacterial agents whose use in therapeutics was hindered by the discovery of antibiotics. Eventually, because of the development and spread of antibiotic resistance among most bacterial species, interest in phage as therapeutic entities has returned, because their noninfectious nature to humans should make them safe for human nanomedicine.This review highlights the most recent advances and progress in phage therapy and bacterial hosts against which phage research is currently being conducted with respect to food, human, and marine pathogens. Bacterial immunity against phages and tactics of phage revenge to defeat bacterial defense systems are also summarized.We have also discussed approved phage-based products (whole phage-based products and phage proteins) and shed light on their influence on the eukaryotic host with respect to host safety and induction of immune response against phage preparations.Moreover, creation of phages with desirable qualities and their uses in cancer treatment, vaccine production, and other therapies are also reviewed to bring together evidence from the scientific literature about the potentials and possible utility of phage and phage encoded proteins in the field of therapeutics and industrial biotechnology.

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Phage Therapy in the Era of Synthetic Biology

Cited by 55 publications

References 114 publications

In Vitro Design and Evaluation of Phage Cocktails Against Aeromonas salmonicida

In Vitro Design and Evaluation of Phage Cocktails Against Aeromonas salmonicida

Transcriptomic and Metabolomics Profiling of Phage–Host Interactions between Phage PaP1 and Pseudomonas aeruginosa

The dawn of phage therapy

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