Bacteriophage Hilla Lee Viener

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BacteriophageHilla Lee Viener
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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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Bacteriophages Classification

• Based on two major criteria
• phage morphology (electron microscopy)
• nucleic acid properties

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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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13 Bacteriophage families
Double stranded DNA, Enveloped
Double stranded DNA, Non-enveloped
SIRV 1, 2
P2
Rudiviridae
Myoviridae
Plasmaviridae
T2
Fuselloviridae
SSV1
TTV1
Tectiviridae
?
PRD1
Siphoviridae
Lipothrixviridae
PM2
P22
Corticoviridae
Podoviridae
Single stranded RNA
Double stranded RNA
Single-stranded DNA
M13 fd
Inoviridae
MS2
phi666
Leviviridae
FX174
Microviridae
Cystoviridae
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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 Virulence Factors Carried On
Phage

• Temperate phage can go through one of two life
  cycles upon entering a host cell.
• Lytic
• Is when growth results in lysis of the host and
  release of progeny phage.
• 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 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 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
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Bacteriophages Lysogenic Cycle
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Bacteriophages Cholera

• 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.

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Bacteriophages Cholera

• 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.

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Bacteriophages CTX Phage

• 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.
• 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.

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Bacteriophages CTX Phage
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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.

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BacteriophageThe Flesh-Eating Bacteria

• 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
• 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.

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BacteriophageThe Flesh-Eating Bacteria

• 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.

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BacteriophageRelatives of Flesh-Eating Bacteria

• Other Group A Streptococci which have acquired
  virulence factors
• Scarlet Fever Toxin
• Streptococcal Toxic Shock Syndrome

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BacteriophageTherapeutic Uses

• 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.

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Any Questions?
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References

• 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. 6295-296
• Waldor, M., and J. Mekalanos. 1996. Lysogenic
  conversion by a filamentous phage encoding
  cholera toxin. Science 2721910-1914
• http//www.evergreen.edu/phage/phagetherapy/phaget
  herapy.html
• http//www.flesheatingbacteria.net/
• http//justice.loyola.edu/klc/BL472/GAS/
• http//www.med.sc.edu85/mayer/phage.htm