Bacteriophage

asifkanth786 3,357 views 33 slides Dec 10, 2016
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bacteriophage


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BACTERIOPHAGE
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Bacteriophage
•A bacteriophage (from 'bacteria and
Greek φαγεν

phagein "to devour") is any one
of a number of viruses that infect bacteria.
They do this by injecting genetic material,
which they carry enclosed in an outer protein
capsid. The genetic material can be ssRNA,
dsRNA, ssDNA, or dsDNA ('ss-' or 'ds-' prefix
denotes single-strand or double-strand) along
with either circular or linear arrangement.
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What are Bacteriophages
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Viruses that attack bacteria were observed by
Twort and d'Herelle in 1915 and 1917. They
observed that broth cultures of certain intestinal
bacteria could be dissolved by addition of a
bacteria-free filtrate obtained from sewage. The
lysis of the bacterial cells was said to be
brought about by a virus which meant a
"filterable poison ("virus" is
Latin for "poison").
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BACTRIOPHAGES
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Bacteriophages typically carry only the genetic
information needed for replication of their
nucleic acid and synthesis of their protein
coats. When phages infect their host cell, the
order of business is to replicate their nucleic
acid and to produce the protective protein coat.
But they cannot do this alone. They require
precursors, energy generation and ribosomes
supplied by their bacterial host cell.
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Bacteriophage
•Bacteriophages
make up a diverse
group of viruses,
some of which have
complex structures,
including double-
stranded DNA.
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Bacteriophage
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BacteriophageBacteriophage
•Also known simply as a
phage; a virus that
attacks and infects
bacteria. The infection
may or may not lead to
the death of the
bacterium, depending on
the phage and sometimes
on conditions. Each
bacteriophage is specific
to one form of bacteria.
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Bacteriophages:
Classification
•At present, over
5000
bacteriophages
have been studied
by electron
microscopy and
can be divided
into 13 virus
families.
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Double stranded
DNA, Enveloped
Double stranded DNA,
Non-enveloped
Myoviridae
Siphoviridae
Podoviridae
P2
T2
λ
P22
TectiviridaePRD1
Corticoviridae
PM2
Single-stranded DNA
Inoviridae
M13 & fd
Microviridae
ΦX174 Leviviridae
Single
stranded
RNA
MS2
Lipothrixviridae
TTV1
FuselloviridaeSSV1
Plasmaviridae
Double
stranded
RNA
phi6
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Cystoviridae
Rudiviridae
SIRV 1, 2
13 Bacteriophage families
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13 Bacteriophage families
Corticoviridae
icosahedral capsid with lipid layer, circular supercoiled
dsDNA
Cystoviridae
enveloped, icosahedral capsid, lipids, three molecules of
linear dsRNA
Fuselloviridae
pleomorphic, envelope, lipids, no capsid, circular
supercoiled dsDNA
Inoviridae genus
(Inovirus/Plectrovirus)
long filaments/short rods with helical symmetry, circular
ssDNA
Leviviridae quasi-icosahedral capsid, one molecule of linear ssRNA
Lipothrixviridae enveloped filaments, lipids, linear dsDNA
Microviridae icosahedral capsid, circular ssDNA
Myoviridae (A-1,2,3) tail contractile, head isometric
Plasmaviridae
pleomorphic, envelope, lipids, no capsid, circular
supercoiled dsDNA
Podoviridae (C-1,2,3) tail short and noncontractile, head isometric
Rudiviridae helical rods, linear dsDNA
Siphoviridae (B-1,2,3) tail long and noncontractile, head isometric
Tectiviridae
icosahedral capsid with, linear dsDNA, "tail" produced for
DNA injection
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Bacteriophages
• Morphology of the T series of Phages
Name Plaque size Head (nm) Tail (nm) Latent period (min) Burst size
T1 medium 50 150 x 15 13 180
T2 small 65 x 80 120 x 20 21 120
T3 large 45 invisible13 300
T4 small 65 x 80 120 x 20 23.5 300
T5 small 100 tiny 40 300
T6 small 65 x 80 120 x 20 25.5 200-300
T7 large 45 invisible13 300
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Cycle of events in Bacteriophage
infecting a Bacterial Cell
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Phage entering a bacterial cellPhage entering a bacterial cell
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Lytic and Lysogenic cycleLytic and Lysogenic cycle
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Bacteriophages:
Virulence Factors Carried On Phage
•Temperate phage can go through one of two life
cycles upon entering a host cell.
1)Lytic:
Is when growth results in lysis of the host and release of
progeny phage.
2)Lysogenic:
Is when growth results in integration of the phage DNA into the
host chromosome or stable replication as a plasmid.
Most of the gene products of the lysogenic phage remains
dormant until it is induced to enter the lytic cycle.
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Lysogenic conversion
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In some interactions between lysogenic phage's
and bacteria, lysogenic conversion may occur. It
is when a temperate phage induces a change in
the phenotype of the bacteria infected that is not
part of a usual phage cycle. Changes can often
involve the external membrane of the cell by
making it impervious to other phages or even by
increasing the pathogenic capability of the
bacteria for a host.
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Examples: of Lysogenic conversion
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* Corynebacterium diphtheria Corynebacterium diphtheria produces the
toxin of diphtheria only when it is infected by the
phage β. In this case, the gene that codes for the
toxin is carried by the phage, not the bacteria.
* Vibrio cholera is a non-toxic strain that can
become toxic, producing cholera toxin, when it is
infected with the phage CTXφ.
* Clostridium botulinum causes botulism.
* Streptococcus pyogenes causes scarlet fever.
* Shiga toxin
* Tetanus
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Bacteriophages:
Lysogenic Conversion
Bacterium Phage
Gene
Product
Phenotype
Vibrio cholerae CTX phage cholerae toxin cholera
Escherichia coli
lambda
phage
shigalike toxin
hemorrhagic
diarrhea
Clostridium botulinum
clostridial
phages
botulinum
toxin
botulism (food
poisoning)
Corynebacterium
diphtheriae
corynephage
beta
diphtheria
toxin
diphtheria
Streptococcus
pyogenes
T12
erythrogenic
toxins
scarlet fever
Examples of Virulence Factors Carried by Phage
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Bacteriophages Uses
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•Used for cloning foreign
genes among other
applications
•Proteins and peptides are
fused to the
Capsid(surface) of the
phage
•The combination of the
phage and peptide is
known as a Fusion Protein
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Bacteriophages causes Lysis of Bacteriophages causes Lysis of
Infected CellsInfected Cells
•The T-phages, T1 through T7, are
referred to as lytic phages because they
always bring about the lysis and death of
their host cell, the bacterium E. coli. T-
phages contain double-stranded DNA as
their genetic material. In addition to their
protein coat or capsid (also referred to as
the "head"), T-phages also possess a tail
and some related structures
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Genetic Engineering Genetic Engineering
BacteriophagesBacteriophages
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•Different sets of genes are
inserted into the genomes of
multiple phages
•These separate phages will
only display one protein,
peptide, or antibody
•Collections of these phages can
comprise Libraries
•These Libraries are exposed to
selected targets and only some
phages will interact with
targets
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Bacteriophages
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Bacteriophages
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•Once these Phages are isolated and
recovered they can be used to infect
bacteria which will create a particle
similar to a monoclonal antibody
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Bacteriophages
•By taking gene segment of
antigens of antibodies and
fusing them to the protein
coat of phages, these
phages will now express the
anti-body in a fusion
protein
•Phage Display Libraries of
antigens can be created to
create anti-body phage
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Bacteriophages in Medicine
•Bacteriophages, or phages, by their very
nature, they can be considered as potential
antibacterial agents. Over the past decade or
two, the idea of phage therapy, i.e. the use of
lytic bacteriophages for both the prophylaxis
and the treatment of bacterial infections, has
gained special significance in view of a
dramatic rise in the prevalence of highly
antibiotic-resistant bacterial strains paralleled
by the withdrawal of the pharmaceutical
industry from research into new antibiotics
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Phage Therapy
•Phages were discovered
to be anti-bacterial agents
and were used throughout
the 1940s in the Soviet
Union for treating
bacterial infections. They
had widespread use
including treating soldiers
in the Red Army.
However, they were
abandoned for general
use in the west for several
reasons:
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Phage Therapy
•Medical trials were
carried out, but a basic
lack of understanding
of phages made these
invalid.
•Phage therapy was
seen as untrustworthy,
because many of the
trials were conducted
on totally unrelated
diseases such as
allergies and viral
infections.
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FDA Approves
•In August 2006, the United States Food and
Drug Administration (FDA) approved LMP-
102 (now List Shield) as a food additive to
target and kill Listeria monocytogenes. LMP-
102 was approved for treating ready-to-eat
(RTE) poultry and meat products. In October of
that year, following the food additive approval
of LMP-102 by Intralytix, the FDA approved a
product by EBI using bacteriophages on
cheese to kill the Listeria monocytogenes
bacteria, giving them GRAS status.
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