Bacteriophage Flashcards
What are bacteriophages?
viruses that infect and kill only bacteria- not mammalian or plant cells
What was the first phage therapy application?
in early 20th centry to treat severe dysentery
Why has there been increased interest in bacteriophages?
antibiotic resistnace
How are bacteriophages commonly used?
antibacterial food additives
Why are bacteriophages useful in the brain?
they are able to cross the BBB- can be used as a therapeutic agent to deliver drugs to the brain
How have bacteriophages been used in neurodegeneration?
can target amyloid which lead to the cloning of hte phage tip and the discovery of the GAIM motif and the engineering to create a fusion protein drug for Alzheimers
What are the 2 groups of bacteriophages?
tailed and filamentous
What type of DNA do tailed bacteriophages have?
dsDNA
What type of DNA do filamentous bacteriophages have?
circular single-stranded DNA
What is the receptor for filamentous phase attachment?
tip of the pilus
What is the coreceptor for filamentous bacteriophages?
TolA-D3
How is a complementary strand of DNA formed once the filamentous DNA is inside the cell?
synthesised by bacterial enzymes
What is the parental replicative form?
a supercoiled dsDNA
What is phage display?
molecular technique for synthesising polypeptides with novel charactersitics
What is the structure of a bacteriophage?
genetic material encapsidated by a protein coat
What are the 2 methods by which phages can infect propagate?
lytic life cycle and lysogenci life cycle
What type of phage has a lysogenic lifecycle?
temperate phages- integrate genome into host and replicate wtih the host for many generations
What is the main advantage of phages in antibacterial therapy?
specificity for target bacteria reduces the damage to normal flora of the host greatly; they evolve naturally to infect the resistant bacteria
What is one of the concerns about the use of phage therapy?
strong antibody response would clear the phages and prevent theri use for extended period of time; narrow host ranges; not always lytic under certain physiological conditions; may impart toxic properties to the bacteria resulting in virulence
How does phage display work?
DNA that encodes the poypeptides is fused with phage coat protein genes adn the desired protein is expressed on the surface of the pahge particle
What can phago display libraries be used for?
screening and isolation of peptides that are highly specific and which have affinity for target proteins- e.g in drug design- acting as an agonist or inhibiting receptor ligand interaction
How haas phage display been used in cocaine addiction?
administered nasally and make their way to CNS when the displayed Fab dragment binds to the cocaine molecule and inhibits its action on the brain
What is phage typing?
use of sensitivity patterns of specific phages for precisely identifying the microbial strains
Why are phages a good potential for gene therapy?
ability to display foreign proteins on their surfaces enables them to target specific cell types
How can phages be used as vehicles for vaccine delivery?
can be used to directly carry the vaccine antignes expressed on their surfaces
What is the benefit of using phages for DNA vaccines?
the coat protects DNA from degradation and as it acts like a virus it would target hte vaccine to APCs
How can antigens be displayed on phage surface in vaccination?
conjugated directly or antigen gene fused to phage coat protein gene
Why are adeno-associated viruses useful for gene therapy?
insert their genetic material at a specific site on chromosome 19
What is cancer gene therapy?
delivery of therapetic genes to tumours e.g cytotoxic genes; tumour suppressor genes
What are the limitations of eukaryotic viral vectors?
undesired uptake by the liver; uptake the reticuloendothelial system; broad tropism and normal tissue toxicity; presence of antiviral neutralising antibodies; yields of production at clinical sclae
What is a new system for targeted systemic gene delivery?
novel hybrid vector- AAV/phage– allows phage to survive in the cell
How have AAVP been used so far?
to eradicate cancer in pet dogs by combinindg AAVP-TNFa to target tumour vasculature
