Phage virus

1. Phase Therapy
Animikha Ghosh
RA2212024010003
Subject-Microbial Genetics
04-05-2023 0

2. What is Phage Virus ?
• Virus that uses bacteria as it’s host
• It has two cycles –Lytic and Lysogenic Cycle
• Lytic bacteriophages have the ability to (a) bind to bacterial receptors, (b) transfer
the genome to bacteria, (c) use bacterial transcription, translation, and replication
to carry out viral replication in the cytoplasm, and (d) release from the host cells.
• Lysogenic bacteriophages are widespread in nature .
• Lysogenic bacteriophages integrate their genes into the host genome after
ingesting host bacteria; these genes can then be passed on to offspring cells
during binary cell division.
• The genes of lysogenic phages have been extracted from the host genome under
conditions of environmental perturbation or other physiological stresses.
• Infected host cells are lysed as a result of these genes' ability to carry out viral
replication in the cytoplasm and produce new offspring virions fast.
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3. Need for Phage Therapy
• The worldwide public health is increasingly under risk from antimicrobial resistance
(AMR).
• This number highlights the present AMR-related difficulties and the pressing need for new,
efficient antimicrobial treatments.
• It is challenging to address the urgent demand for novel therapeutic agents against AMR
because a large number of pharmaceutical companies no longer produce new antibiotics.
• Although bacteriophage therapy is not a novel form of therapy, it continues to hold out
some promise in the fight against AMR.
• The Wellcome Trust hired 24 academic and industrial experts in 2017 to draught a historic
report that would identify potential therapeutic antibiotic substitutes.
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4. Advantages of Phage therapy
Bactericidal
agents
Formulation
and applicable
universality
Reproductive
capacity
Differentiated
toxicity
Lack of cross-
resistance with
antibiotics
Rapid
discovery
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5. Disadvantages of Phage therapy
Safety Self-renewal
Stability
Bacteriophage-
resistance
mutants
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6. Bacteriophages cocktail therapy
• Monotherapy not sufficient
• Bacteriophage cocktails can be directed to battle only a single bacterial strain, multiple
strains of a single bacterial species, or even multiple species
• Bacteriophage can be used in sequence
• Pyo bacteriophage (Pyo) and intestibacteriophage
• Pyo has been used in the treatment of suppurative and intestinal
diseases against S. aureus, Escherichia coli, Pseudomonas aeruginosa, Proteus
vulgaris, Proteus mirabilis, and Streptococcus pyogenes
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7. Liposome-encapsulated Bacteriophages
• The poor stability of phages in gastric acid conditions and insufficient retention time in the
intestine are the two main problems for the low therapeutic efficiency of oral phages,
requiring the frequent administration of free phages.
• Frequent administration is time-consuming and expensive, resulting in poor patient
compliance
• We can optimise Liposome encapsulation by the use of cationic liposome
• attaching particular targeting ligands to the surfaces of liposomes
• increasing the in vivo circulation time and slowing the release of contents
• encapsulating various probes to monitor the pharmacokinetics of liposome-loaded
bacteriophages
• changing the charge distribution of liposomes to prolong the retention time
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8. Polymer Encapsulation
• pH conditions
• pepsin, protease, lipase, amylase, and trypsinogen
• Bile salts
• the retention time of distinct intestinal segments, such as the
duodenum and ileum
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9. Bacteriophage-derived Therapeutic
Proteins
• Some of the crucial proteins and enzymes used to destroy bacterial cells during infection
are encoded by the bacteriophage genomes.
• peptidoglycan hydrolases and polysaccharide depolymerizing enzymes
• Peptidoglycan hydrolases are usually located in the outermost layer of the phage protein shells,
which is the structural component of the virus and acts on the local degradation of the
peptidoglycan layer so that the bacteriophage tail tube structure ejects its genome into the host
• Polysaccharide depolymerizing enzymes, which can degrade polysaccharose components on the
surface of the bacterial cell membrane, such as Gram-negative lipopolysaccharides, are also
encoded by bacteriophages
• The depolymerase of bacteriophages digests the polysaccharides on the cell membrane
of bacteria, thereby facilitating the bacteriophages in entering the host receptors; they
may degrade biofilms
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10. Potential Treatments For Burn Wound
Infection
• P. aeruginosa
• K. pneumoniae
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