Bacteriophages, or phages, are viruses that infect bacteria. They have either a lytic or lysogenic lifecycle. The lytic cycle involves the phage hijacking the host cell to replicate its DNA and proteins before lysing the cell. The lysogenic cycle incorporates the phage DNA into the host genome where it remains dormant until stress induces the lytic cycle. Phages have either DNA or RNA genomes encapsulated in protein capsids and may have complex or simple structures like tails. They are ubiquitous wherever bacteria exist and are the most abundant biological entity on Earth.
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Phages.pptx
1. Phage/bacteriophage
It is a virus that infects and replicates within bacteria and archaea
The term was derived from "bacteria" and the Greek φαγεῖν (phagein), meaning
"to devour” [devour = eat (food or prey) hungrily or quickly]
Composed of proteins that encapsulate a DNA or RNA genome,
and may have structures that are either simple or elaborate
Among the most common and diverse entities in the biosphere.
Ubiquitous viruses, found wherever bacteria exist
Estimate: >1031 bacteriophages on the planet, >every other
organism on earth, including bacteria, combined
Viruses are the most abundant biological entity in the water column of the
world's oceans, and the second largest component of biomass after prokaryotes,
Up to 9x108 virions per millilitre have been found in microbial mats at the
surface and up to 70% of marine bacteria may be infected by phages
Ernest Hanbury Hankin reported (in 1896) that something in the waters of
the Ganges and Yamuna rivers in India - a marked antibacterial action
against cholera and it could pass through a very fine porcelain filter
[He noted in 1896 that boiling water supplies was a reliable protection against cholera in India; unboiled
water of the Ganges kills the cholera germ in less than 3 hours; the same water, when boiled, does not have
the same effect; He suggested that it was responsible for limiting the spread of cholera; it could pass
through a very fine porcelain filter]
Ernest Hanbury Hankin
2. Phage/bacteriophage
In 1915, British bacteriologist Frederick Twort, superintendent of the Brown
Institution of London, discovered a small agent that infected and killed bacteria
Twort believed the agent must be one of the following:
-a stage in the life cycle of the bacteria
-an enzyme produced by the bacteria themselves, or
-a virus that grew on and destroyed the bacteria
Twort's research was interrupted by the onset of World War I as well as a
shortage of funding and the discoveries of antibiotics
Independently, French-Canadian microbiologist Félix d'Hérelle, working at
the Pasteur Institute in Paris, announced on 3 September 1917, that he had
discovered "an invisible, antagonistic microbe of the dysentery bacillus”
It was d'Herelle who conducted much research into bacteriophages and
introduced the concept of phage therapy; Credit for discovery: Twort and de
Herelle
Left panel - Frederick William Twort
Right panel - Félix d'Herelle and
George Eliava (Phage therapy)
Term Bacteriophage was coined by
Félix d’Hérelle
3. Phage/bacteriophage
A typical phage exist in two phases:
extracellular phase, mature infectious particle – virion
intracellular phase – exist in the form of NA within the host bacteria and
replicate along with the host bacterium – prophage
General characteristics of phage:
The virus that infects only bacterial cells (bacteria eater)
[can infect a single species of bacteria or even specific strains of bacteria within a
species]
Known as naturally abundant obligate intracellular parasites
[are obligate intracellular parasites that remain latent outside the host cell and
require host cellular machinery to conduct their metabolic activities]
Niche- present where bacteria or archaea reside
Diversity is more than the number of bacteria in nature
Small size causes it to beyond the limits of light microscope resolution
Smallest bacteriophage: 20 nanometers in diameter, largest bacteriophage: 500
nanometers in diameter
Phage therapy, viral phage therapy, or phagotherapy is the therapeutic use
of bacteriophages for the treatment of pathogenic bacterial infections
4. Phage/bacteriophage
Structure
The basic structure of all bacteriophages is the same. They consist of a core of
nuclear material surrounded by a protein capsid
Bacteriophages exist in three basic structural forms; an icosahedral head with a
tail, an icosahedral head without a tail, and a filamentous form
The genetic material or nuclear material of bacteriophages can be either DNA or
RNA, both of which can either be double-stranded or single-stranded
The genome can be one or multipartite and is located inside the phage capsid
The shape of viruses is closely related to their genome, and a large genome
indicates a large capsid and therefore a more complex organisation
The most studied group – tailed phages (order Caudovirales) which are classified
by the type of tail; Siphoviridae – a long non-contractile tail, Podoviridae – a short
non-contractile tail and Myoviridae – a complex contractile tail
5. Phage/bacteriophage
Structure
The most studied group is that of tailed phages with a dsDNA genome, and it
also represents the largest group
The tailed phages have three major components: i) a capsid where the genome
is packed, ii) a tail that serves as a pipe during infection to secure transfer of
genome into host cell and iii) a special adhesive system (adsorption apparatus) at
the very end of the tail that will recognise the host cell and penetrate its wall
The functional phage is a result of a multistep process that starts with all the
necessary proteins produced by the host cell after infection: capsid, portal, tail,
scaffolding, terminase, etc.
The capsids of the dsDNA phages often have fivefold or icosahedral symmetries
Electron micrograph of a
negatively stained
Acinetobacter baumannii
phage (a) and generalised
structure of a tailed phage
(b)
10. Fig.: (A) Representation of prokaryote bacteriophage morphotypes. (B) Members of the
Order Caudovirales
11. Phage/bacteriophage
Life cycle
The overall process of the entry of the virus, its replication, and exit from the
host cell comprises the lifecycle of viruses
There are two types of lifecycles that differ in the mechanism of DNA replication
where, in one, the viral DNA is incorporated into the host DNA, but in the other,
the DNA replicates separately from the host DNA
1. Lytic Cycle
The viral DNA remains as a free-floating molecule and replicates separately from
the bacterial DNA.
The lytic cycle usually occurs in virulent phages as the phages result in the
destruction of the infected cell membrane during the release of the viral particles.
The lytic cycle is a virulent infection as it results in the destruction of a cell
12.
13. a) Attachment and Penetration
The first step in the lifecycle of a bacteriophage is attachment, where the ligands
on specific molecules on the surface of the viral particles bind to the receptor
molecules on the plasma membrane of the host cell.
The receptors depend on the type of viruses as most orthomyxoviruses use
receptors like terminal sialic acid on an oligosaccharide side chain of a cellular
glycoprotein.
The ligand, however, is an aperture at the distal end of each monomer of the
trimeric viral hemagglutinin glycoprotein.
Even though there is a high degree of specificity between the receptors and the
ligands, a number of viruses might use the same receptors.
Besides, some bacteriophages might use other membrane glycoproteins as their
receptors.
Once attached, the virus injects its nuclear material into the cytoplasm of the
bacterial cell.
The viral genome (either DNA or RNA) remains in the cytoplasm, and in some
cases becomes circular and resemble the bacterial plasmid.
b) Biosynthesis and Transcription
Once in the cytoplasm, the viral genome hijacks the host cellular mechanism and
utilizes it to produce more viruses.
14. b) Biosynthesis and Transcription
In the case of DNA viruses, the DNA undergoes transcription to produce
messenger RNA that then directs the ribosome of the host cell.
In the case of the lytic cycle, the mRNA encodes for various polypeptides, the
first of which destroy the host’s DNA.
In the case of RNA viruses, an enzyme called reverse transcriptase is involved
which transcribes the viral RNA into DNA.
The DNA is then transcribed back to mRNA, which then directs the destruction
of host DNA.
The viral DNA then takes control of the host cell and produces different proteins
required for the assembly of new viruses.
The viral DNA also undergoes replication to produce more genetic material for
new viral particles.
The process of biosynthesis and DNA replication is mediated by different genes
and enzymes.
c) Assembly and Lysis
As biosynthesis and replication continue, a large number of viral proteins and
genomes are formed.
Once enough viral particles are formed and matured, these particles under
assembly during which the genetic material of the virus is incorporated into the
viral protein, capsid.
15. c) Assembly and Lysis
The newly assembled bacteriophages release the enzyme, lysin, into the
cytoplasm. The enzyme causes the lysis of the bacterial cell wall, resulting in the
release of newly formed phage particles.
Thus, at the end of the lytic lifecycle, the infected bacterial cell and cell
membrane are destroyed.
1. Lysogenic Cycle
Lysogenic is one of the two lifecycles of bacteriophages defined by the
incorporation of the bacteriophage genome into the host genome.
During the lysogenic lifecycle, the host bacteria continue to live and reproduce
normally after the replication of bacteriophages.
The genetic material of bacteriophage incorporated in the bacterial DNA during
the lysogenic lifecycle is called a prophage which can be transmitted to daughter
cells during the bacterial cell division.
The lysogenic cycle is a temperate and non-virulent infection as the
bacteriophage doesn’t kill the host cell.
a) Attachment and Penetration
The first step of the lysogenic lifecycle is identical to the first step of the lytic
lifecycle.
The bacteriophage ligands attach to the receptors on the surface of the bacterial
cell wall.
16.
17. 1. Lysogenic Cycle
a) Attachment and Penetration
The attachment is highly specific as it is determined by the interaction between
the ligands and the receptors present on the surface of the bacterial cell wall.
After attachment, the viral genome is injected into the cytoplasm of the host
cell.
The infective viral DNA or prophage is then incorporated into the host
chromosome, which converts the infective prophage into a non-infective
prophage.
b) Replication
The viral DNA then uses the host machinery to replicate as it continues to
replicate with the host chromosomes during cell division.
In some cases, the prophage might be ejected from the host chromosome, and
the viral DNA might enter the lytic cycle.
Unlike the lytic cycle, the bacterial cellular mechanism is not hijacked by the viral
particles, and no biosynthesis of viral proteins takes place.
The prophage, however, can be transferred to the daughter cells during the
bacterial cell division.
The process of replication continues until there are some stressors which can
either be physical stressors like UV radiation, low nutrient condition or chemical,
which might result in the transition of the lysogenic cycle into the lytic cycle.
18. 1. Lysogenic Cycle
b) Replication
Once converted into the lytic cycle, the viral DNA undergoes transcription to
produce viral proteins. The proteins and viral genome are then assembled to form
complete viral particles which then are released from the host cell by lysis.
Assembly pathway
Assembly pathway of phages.
Multiple copies of the
capsid/scaffold complex bind the
portal protein to form the
procapsid; then, the scaffold
proteins are ejected, and DNA is
packaged into the procapsid,
which expands to the size of the
mature capsid. The head
completion proteins (the stopper
and the adaptor) are bound to the
portal complex preventing DNA
leakage. Next, decoration proteins
bind to the capsid, and the tail,
assembled separately or after DNA
packaging, is attached; thus, the
final infectious phage is produced.
The preassembled tail attaches in
Myoviridae and Siphoviridae, while
in Podoviridae the tail assembles
at the stopper
19. Lytic Cycle vs Lysogenic Cycle
Characteristics Lytic Cycle Lysogenic Cycle
Definition
The lytic cycle is a type of
lifecycle of bacteriophages
where the viral DNA remains as
a free-floating molecule and
replicates separately from the
bacterial DNA.
Lysogenic is another type of lifecycle
of bacteriophages which is defined
by the incorporation of the
bacteriophage genome into the host
genome.
Also called
The lytic cycle is also called the
infective cycle or virulent cycle.
The lysogenic cycle is also called a
temperate cycle or non-virulent
cycle.
Viral DNA
In the lytic cycle, the viral DNA
remains in the cytoplasm of the
host cell.
In the lysogenic cycle, the viral DNA
is incorporated into the host
chromosome.
Prophage
No prophage is present in the
lytic cycle.
The lysogenic cycle consists of a
prophage stage.
Host DNA
Host DNA is destroyed by various
proteins encoded by the viral
DNA.
The host DNA is not affected by the
viral DNA.
Viral replication
The viral DNA replication occurs
separately from the host DNA
replication.
Viral DNA replication occurs along
with the host DNA replication.
20. Characteristics Lytic Cycle Lysogenic Cycle
The productivity of viral
DNA
The productivity of viral DNA
and viral proteins is high.
The productivity of viral DNA and viral
proteins is low.
Host cellular mechanism
Host cellular mechanism is
completely hijacked by the viral
DNA.
Host cellular mechanisms remain
unaffected.
Duration
The lytic cycle is immediate and
is completed within a short
period of time.
The lysogenic cycle takes a longer
period of time.
Transition
The lytic cycle cannot transition
into a lysogenic cycle.
The lysogenic cycle can transition
into the lytic cycle.
Infection
As the cycle is an infective
cycle, symptoms of viral
infections can be observed.
The cycle is a non-infective cycle that
doesn’t result in symptoms.
Transfer
The viral DNA cannot be
transferred from the host cell
to the daughter cell during the
lytic cycle.
The viral DNA can be transferred into
the daughter cell during the lysogenic
cycle.
Genetic recombination
The lytic cycle doesn’t allow
genetic recombination of the
host chromosome.
The lysogenic cycle allows the genetic
recombination of the host
chromosome.
Lysis of host cell
The lytic cycle ends with the
lysis of the host cell.
The lysogenic cycle doesn’t result in
the lysis of the host cell.