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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

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Bacteriophages under Electron Microscope

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Bacteriophage (Phage)

Definition - Obligate intracellular parasites that multiply inside bacteria by making use of some or all of the host biosynthetic machinery

SignificanceModels for animal cell virusesGene transfer in bacteriaMedical applications

Identification of bacteria - phage typing Treatment and prophylaxsis???

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Bacteriophages: Definition & History

Bacteriophages are viruses that can infect and destroy bacteria.

They have been referred to as bacterial parasites, with each phage type depending on a single strain of bacteria to act as host.

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BACTRIOPHAGES

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Like most viruses, bacteriophages typically carry only the genetic

information needed for replication of their nucleic acid and synthesis of their protein

coats.. They require precursors, energy generation and ribosomes supplied by their bacterial host

cell.

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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BacteriophageBacteriophages make up a diverse group of viruses, some of which have complex structures, including double-stranded DNA.

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BacteriophageBacteriophage

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BacteriophageBacteriophageAlso 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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Composition and StructureCompositionComposition

Nucleic acidNucleic acidGenome sizeGenome sizeModified Modified

basesbasesProteinProtein

ProtectionProtectionInfectionInfection

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• Structure (T4)

– Size– Head or

capsid– Tail

Tail

Tail Fibers

Base Plate

Head/Capsid

Contractile Sheath

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Phage entering a bacterial cellPhage entering a bacterial cell

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Bacteriophage showing Lytic 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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Bacteriophages: Lysogenic Conversion

Some lysogenic phage carry genes that can enhance the virulence of the bacterial host. For example, some phage carry genes that For example, some phage carry genes that

encode toxins.encode toxins.

These genes, once integrated into the bacterial chromosome, can cause the once harmless bacteria to release potent toxins that can cause disease.

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Bacteriophages

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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

Bacteriophages

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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

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

Lytic and Lysogenic cycle

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Bacteriophages: Lysogenic Conversion

Bacterium PhageGene

ProductPhenotype

Vibrio cholerae CTX phage cholerae toxin cholera

Escherichia colilambda phage

shigalike toxinhemorrhagic

diarrhea

Clostridium botulinumclostridial phages

botulinum toxin

botulism (food poisoning)

Corynebacterium diphtheriae

corynephage beta

diphtheria toxin

diphtheria

Streptococcus pyogenes

T12erythrogenic

toxinsscarlet fever

Examples of Virulence Factors Carried by Phage

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Lysogenic conversion

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In some interactions between lysogenic phages 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.

Assay for Lytic Phage

• Plaque assay

– Method– Plaque forming unit

(pfu)– Measures infectious

particles

Bacteria

Phage

+Phage

Plaque assayMethodPlaque forming unit (pfu)

Measures infectious particles

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04/17/23 31Figure 13.10.1

Attachment:Attachment:Phage Phage attaches to attaches to host cell.host cell.

Penetration:Phage pnetrates host cell and injects its DNA.

Merozoites released into bloodsteam from liver may infect new red blood cells

1

2

3

Bacterial Bacterial cell wallcell wall

Bacterial chromosome

Capsid DNA

Capsid

Sheath

Tail fiber

Base platePin

Cell wall

Tail

Plasma membrane

Sheath contracted

Tail core

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4 Maturation:Maturation:Viral components Viral components

are assembled are assembled into virions.into virions.

Tail

5 Release:Release:Host cell lyses Host cell lyses

and new virions and new virions are released.are released.

DNA

Capsid

Tail fibers

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Examples:Examples:

* 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 cholerae 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

Medical Applications of Phages“I strongly believe phage could become an effective antibacterial tool” - Carl Merril, Chief of the Laboratory of Biochemical Genetics, National Institute of Mental Health, NIH.“It might be another string on the bow, such that when (conventional antibiotics) fail, here’s something that has a chance of working. But it’s not going to be a panacea” - Joshua Lederberg, Sackler Foundation Scholar at The Rockefeller University

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