Bacteriophage
Hilla Lee Viener
Bacteriophages:
Definition & History
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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.
Bacteriophages:
Classification
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Based on two major criteria:
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phage morphology (electron
microscopy)
nucleic acid properties
Bacteriophages:
Classification
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At present, over 5000
bacteriophages have
been studied by
electron microscopy
and can be divided
into 13 virus families.
13 Bacteriophage families
Double stranded DNA,
Non-enveloped
P2
T2
Fuselloviridae SSV1
λ
Tectiviridae
Plasmaviridae
TTV1
PRD1
Lipothrixviridae
Corticoviridae PM2
P22
Podoviridae
Single-stranded DNA
Inoviridae
SIRV 1, 2
Rudiviridae
Myoviridae
Siphoviridae
Double stranded
DNA, Enveloped
M13 & fd
Single
stranded
RNA
Double
stranded
RNA
MS2
Microviridae ΦX174
phi666
Leviviridae
Cystoviridae
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
Bacteriophages:
Virulence Factors Carried On Phage
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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.
Bacteriophages:
Lysogenic Conversion
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Some lysogenic phage carry genes that
can enhance the virulence of the bacterial
host.
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For example, some phage carry genes that encode
toxins.
These genes, once integrated into the
bacterial chromosome, can cause the
once harmless bacteria to release potent
toxins that can cause disease.
Bacteriophages:
Lysogenic Conversion
Examples of Virulence Factors Carried by Phage
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
Bacteriophages:
Lysogenic Cycle
Bacteriophages:
Cholera
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The effect of lysogenic conversion can be seen
clearly in the disease cholera.
Cholera is caused by a Gram negative, curved
rod called Vibrio cholerae.
The bacterium is transmitted through
contaminated water and results in severe
diarrhea and rapid dehydration of the infected
person.
The most effective treatment involves
intravenous or oral liquid replacement therapy.
Bacteriophages:
Cholera
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Vibrio cholerae did not always cause disease.
Infection with the CTX phage gives the bacterium
its toxinogenicity. (cholerae toxin)
The phage recognizes a pilus on the surface of
the bacterium and uses it to enter the cell.
Once inside the cell, the CTX phage integrates
into the chromosome and the lysogen expresses
cholera toxin.
Bacteriophages:
CTX Phage
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The CTX phage has received special attention because it is
the first filamentous phage found to transfer toxin genes
to its host.
The ability to transfer virulence genes by phage has
important implications on the development of vaccines
against bacteria.
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For example, some of the first vaccines tested against V.
cholera had a chromosomal deletion of the gene encoding
cholera toxin.
This resulted in a bacterium that was nonvirulent, and thus
was useful for human vaccines.
However, the vaccine strain could readily acquire a
functional copy of the cholera toxin gene by infection with
CTX phage, turning an innocent vaccine strain into a fully
virulent strain.
Bacteriophages:
CTX Phage
Bacteriophages:
Cholera
Vibrio cholerae and other pathogens
(diarrheal diseases). Caused 2.5 million
deaths from cholera and other diarrheal
diseases in 1997. Contaminated water and
foods are primary vectors. Most victims
are under five years of age and live in
developing countries. Death preventable
with oral rehydration therapy, proper
nutrition, and antibiotics.
Followed by AIDS with 2.3 million deaths
in 1997.
Bacteriophage:
The Flesh-Eating Bacteria
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Necrotizing fasciitis, the flesh-eating bacteria, is really just
a Group A Streptococcal infection.
This bacteria is the same as the one that causes “strep
throat.”
Some strains have acquired new virulence factors and code
for exotoxins and hemolysins.
There are two new exotoxins:
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A protease that degrades host cell proteins.
A "superantigen" that so excites the immune systems that it
causes healthy cells to commit suicide (cytokines,
programmed cell death, apoptosis).
It is contacted from aerosols released by a sneeze or
cough of a Strep A infected individual.
If it enters the body through a cut or abrasion on the skin,
then it may infect the fascial tissue between the skin and
the muscles.
Bacteriophage:
The Flesh-Eating Bacteria
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Then it rapidly kills tissues causing gangrene conditions.
If treat early with antibiotics and removal of infected tissue
then amputation and death can be averted.
There are between 500-1500 case in the U.S.A. each year
Flesh-eating bacteria has a death rate of 20-50%.
Bacteriophage:
Relatives of Flesh-Eating Bacteria
Other Group A Streptococci which have acquired virulence factors:
 Scarlet Fever Toxin
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Streptococcal Toxic Shock Syndrome
Bacteriophage:
Therapeutic Uses
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Bacteriophage has also been used to fight many bacterial infections.
Some examples of diseases treated with phage therapy:
 staphylococcal skin disease
 skin infections caused by Pseudomonas
 Klebsiella
 Proteus
 E. coli
 P. aeruginosa infections in cystic fibrosis patients
 neonatal sepsis
 surgical wound infections
Likewise, bacteriophage has also been used to treat animal disease.
Any Questions?
References
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Brock, T. 1997. Biology of Microorganisms, Prentice Hall, NJ.
Calendar, R. 1988. The Bacteriophages, Volume 2, Plenum Press, NY,
pp.683-715.
Salyers, A., and D. Whitt. 1994. Bacterial Pathogenesis: A Molecular
Approach, ASM Press, Washington D.C. pp.141-155,169-181.
Waldor, M. 1998. Bacteriophage biology and bacterial virulence.
Trends Microbiol. 6:295-296
Waldor, M., and J. Mekalanos. 1996. Lysogenic conversion by a
filamentous phage encoding cholera toxin. Science 272:1910-1914
http://www.evergreen.edu/phage/phagetherapy/phagetherapy.html
http://www.flesheatingbacteria.net/
http://justice.loyola.edu/~klc/BL472/GAS/
http://www.med.sc.edu:85/mayer/phage.htm