In Vitro Characteristics of Phages to Guide ‘Real Life’ Phage Therapy Suitability
Abstract
:1. Introduction
2. Phage Isolation
3. Characterization of Phages for Phage Therapy Applications
3.1. Genomic and Morphological Characteristics
3.2. Host Receptor Identification
3.3. Stable Storage, Administration and Effectiveness in Trials
4. Phage Particles Versus Phage-Derived Products
5. Overcoming Host-Encoded Phage-Resistance Mechanisms
5.1. DNA Degradation by R-M Systems
5.2. DNA Degradation by CRISPR-Cas Systems
5.3. Prevention of Adsorption
5.4. Cocktails—the Power of Many
5.5. Combination Therapy
6. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Resistance Mechanism | Method of Bypass | Application | Reference(s) |
---|---|---|---|
Restriction modification | Phage-encoded methyltransferases | Protein homology query for identification in candidates | [89] |
Enhancement of host methylation | Protein homology query for identification in candidates | [90,91] | |
Base modification | Protein homology query for identification in candidates | [92,93] | |
CRISPR | Mutation of protospacers | High MOI to encourage mutation of protospacers | [94,95,96] |
Phage-encoded anti CRISPR systems | Protein homology query for identification in candidates | [97,98,99,100] | |
Prevention of adsorption | Mutation of receptor binding protein | High MOI to encourage mutation in RBP | [40,101] |
Selection of multiple RBP type phages | Target a diverse range of receptors on target surface | [102] | |
Biofilm | Antibiotic combination therapy | Dual-pronged inhibition of target decreasing likelihood of resistance emergence | [103,104,105,106,107] |
Emergence of phage resistant variants | Informed cocktail development (SBS method, serial enrichment) | Selection of phages capable of infecting “future” resistant variants | [13,108] |
Selection of multiple phages infecting a single strain | Target a diverse range of receptors on target surface | [12,109,110] |
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Casey, E.; Van Sinderen, D.; Mahony, J. In Vitro Characteristics of Phages to Guide ‘Real Life’ Phage Therapy Suitability. Viruses 2018, 10, 163. https://doi.org/10.3390/v10040163
Casey E, Van Sinderen D, Mahony J. In Vitro Characteristics of Phages to Guide ‘Real Life’ Phage Therapy Suitability. Viruses. 2018; 10(4):163. https://doi.org/10.3390/v10040163
Chicago/Turabian StyleCasey, Eoghan, Douwe Van Sinderen, and Jennifer Mahony. 2018. "In Vitro Characteristics of Phages to Guide ‘Real Life’ Phage Therapy Suitability" Viruses 10, no. 4: 163. https://doi.org/10.3390/v10040163