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BacteriophageBacteriophageHilla Lee VienerHilla Lee Viener
Bacteriophages: Bacteriophages: Definition & HistoryDefinition & History
Bacteriophages are Bacteriophages are viruses that can infect viruses that can infect and destroy bacteria.and destroy bacteria.
They have been They have been referred to as bacterial referred to as bacterial parasites, with each parasites, with each phage type depending phage type depending on a single strain of on a single strain of bacteria to act as host. bacteria to act as host.
Bacteriophages: Bacteriophages: ClassificationClassification
Based on two major Based on two major criteriacriteria::
phage morphology (electron phage morphology (electron microscopy)microscopy)
nucleic acid propertiesnucleic acid properties
Bacteriophages: Bacteriophages: ClassificationClassification
At present, over At present, over 5000 5000 bacteriophages bacteriophages have been studied have been studied by electron by electron microscopy and can microscopy and can be divided into 13 be divided into 13 virus families. virus families.
Double stranded DNA, Enveloped
Double stranded DNA,Non-enveloped
Myoviridae
Siphoviridae
Podoviridae
P2
T2
λ
P22
Tectiviridae PRD1
Corticoviridae PM2
Single-stranded DNA
Inoviridae M13 & fd
Microviridae ΦX174 Leviviridae
Single strande
d RNAMS2
Lipothrixviridae
TTV1
FuselloviridaeSSV1Plasmaviridae
Double stranded RNA
phi666
Cystoviridae
RudiviridaeSIRV 1, 2
13 Bacteriophage families
13 Bacteriophage families
Corticoviridaeicosahedral capsid with lipid layer, circular supercoiled
dsDNA
Cystoviridaeenveloped, icosahedral capsid, lipids, three molecules of
linear dsRNA
Fuselloviridaepleomorphic, 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
Plasmaviridaepleomorphic, 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
Tectiviridaeicosahedral capsid with, linear dsDNA, "tail" produced for
DNA injection
Bacteriophages: Bacteriophages: Virulence Factors Carried On Virulence Factors Carried On
PhagePhage Temperate phage can go through one Temperate phage can go through one
of two life cycles upon entering a host of two life cycles upon entering a host cell.cell.
1)1) Lytic:Lytic:Is when growth results in lysis of the host and Is when growth results in lysis of the host and release of progeny phage.release of progeny phage.
2)2) Lysogenic:Lysogenic:Is when growth results in integration of the Is when growth results in integration of the phage DNA into the host chromosome or stable phage DNA into the host chromosome or stable replication as a plasmid. replication as a plasmid.
Most of the gene products of the lysogenic Most of the gene products of the lysogenic phage remains dormant until it is induced to phage remains dormant until it is induced to enter the lytic cycle. enter the lytic cycle.
Bacteriophages: Bacteriophages: Lysogenic ConversionLysogenic Conversion
Some lysogenic phage carry genes Some lysogenic phage carry genes that can enhance the virulence of that can enhance the virulence of the bacterial host.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 These genes, once integrated into the bacterial chromosome, can the bacterial chromosome, can cause the once harmless bacteria to cause the once harmless bacteria to release potent toxins that can cause release potent toxins that can cause disease. disease.
Bacteriophages: Bacteriophages: Lysogenic ConversionLysogenic Conversion
Examples of Virulence Factors Carried by PhageExamples of Virulence Factors Carried by Phage
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
Bacteriophages: Bacteriophages: Lysogenic CycleLysogenic Cycle
Bacteriophages: Bacteriophages: CholeraCholera
The effect of lysogenic conversion can be The effect of lysogenic conversion can be seen clearly in the disease cholera. seen clearly in the disease cholera.
Cholera is caused by a Gram negative, Cholera is caused by a Gram negative, curved rod called curved rod called Vibrio choleraeVibrio cholerae..
The bacterium is transmitted through The bacterium is transmitted through contaminated water and results in severe contaminated water and results in severe diarrhea and rapid dehydration of the diarrhea and rapid dehydration of the infected person. infected person.
The most effective treatment involves The most effective treatment involves intravenous or oral liquid replacement intravenous or oral liquid replacement therapy. therapy.
Bacteriophages: Bacteriophages: CholeraCholera
Vibrio choleraeVibrio cholerae did not always cause did not always cause disease. disease.
Infection with the CTX phage gives the Infection with the CTX phage gives the bacterium its toxinogenicity. (cholerae bacterium its toxinogenicity. (cholerae toxin)toxin)
The phage recognizes a pilus on the The phage recognizes a pilus on the surface of the bacterium and uses it to surface of the bacterium and uses it to enter the cell. enter the cell.
Once inside the cell, the CTX phage Once inside the cell, the CTX phage integrates into the chromosome and the integrates into the chromosome and the lysogen expresses cholera toxin.lysogen expresses cholera toxin.
Bacteriophages: Bacteriophages: CTX PhageCTX Phage
The CTX phage has received special attention The CTX phage has received special attention because it is the first because it is the first filamentous phagefilamentous phage found to found to transfer toxin genes to its host. transfer toxin genes to its host.
The ability to transfer virulence genes by phage has The ability to transfer virulence genes by phage has important implications on the development of important implications on the development of vaccines against bacteria. vaccines against bacteria.
For example, some of the first vaccines tested against For example, some of the first vaccines tested against V. cholera had a chromosomal deletion of the gene V. cholera had a chromosomal deletion of the gene encoding cholera toxin. encoding cholera toxin.
This resulted in a bacterium that was nonvirulent, This resulted in a bacterium that was nonvirulent, and thus was useful for human vaccines.and thus was useful for human vaccines.
However, the vaccine strain could readily acquire a However, the vaccine strain could readily acquire a functional copy of the cholera toxin gene by functional copy of the cholera toxin gene by infection with CTX phage, turning an innocent infection with CTX phage, turning an innocent vaccine strain into a fully virulent strain. vaccine strain into a fully virulent strain.
Bacteriophages: Bacteriophages: CTX PhageCTX Phage
Bacteriophages: Bacteriophages: CholeraCholera
Vibrio cholerae and other pathogens Vibrio cholerae and other pathogens (diarrheal diseases). Caused 2.5 million (diarrheal diseases). Caused 2.5 million deaths from cholera and other diarrheal deaths from cholera and other diarrheal diseases in 1997. Contaminated water diseases in 1997. Contaminated water and foods are primary vectors. Most and foods are primary vectors. Most victims are under five years of age and victims are under five years of age and live in developing countries. Death live in developing countries. Death preventable with oral rehydration preventable with oral rehydration therapy, proper nutrition, and therapy, proper nutrition, and antibiotics. antibiotics. Followed by AIDS with 2.3 million Followed by AIDS with 2.3 million deaths in 1997.deaths in 1997.
Bacteriophage:Bacteriophage:The Flesh-Eating BacteriaThe Flesh-Eating Bacteria
Necrotizing fasciitis, the flesh-eating bacteria, is Necrotizing fasciitis, the flesh-eating bacteria, is really just a Group A Streptococcal infection.really just a Group A Streptococcal infection.
This bacteria is the same as the one that causes This bacteria is the same as the one that causes “strep throat.”“strep throat.”
Some strains have acquired new virulence factors Some strains have acquired new virulence factors and code for exotoxins and hemolysins.and code for exotoxins and hemolysins.
There are two new exotoxins:There are two new exotoxins: A A proteaseprotease that degrades host cell proteins. that degrades host cell proteins. A "superantigen" that so excites the immune systems A "superantigen" that so excites the immune systems
that it causes healthy cells to commit suicide that it causes healthy cells to commit suicide (cytokines, programmed cell death, apoptosis). (cytokines, programmed cell death, apoptosis).
It is contacted from aerosols released by a sneeze It is contacted from aerosols released by a sneeze or cough of a Strep A infected individual.or cough of a Strep A infected individual.
If it enters the body through a cut or abrasion on If it enters the body through a cut or abrasion on the skin, then it may infect the fascial tissue the skin, then it may infect the fascial tissue between the skin and the muscles.between the skin and the muscles.
Bacteriophage:Bacteriophage:The Flesh-Eating BacteriaThe Flesh-Eating Bacteria
Then it rapidly kills tissues causing gangrene Then it rapidly kills tissues causing gangrene conditions.conditions.
If treat early with antibiotics and removal of infected If treat early with antibiotics and removal of infected tissue then amputation and death can be averted. tissue then amputation and death can be averted.
There are between 500-1500 case in the U.S.A. each There are between 500-1500 case in the U.S.A. each yearyear
Flesh-eating bacteria has a death rate of 20-50%.Flesh-eating bacteria has a death rate of 20-50%.
Other Group A Streptococci which have acquired virulence Other Group A Streptococci which have acquired virulence factors:factors:
Scarlet Fever ToxinScarlet Fever Toxin
Streptococcal Toxic Shock SyndromeStreptococcal Toxic Shock Syndrome
Bacteriophage:Bacteriophage:Relatives of Flesh-Eating BacteriaRelatives of Flesh-Eating Bacteria
Bacteriophage has also been used to fight many bacterial Bacteriophage has also been used to fight many bacterial infections. infections. Some examples of diseases treated with phage therapy:Some examples of diseases treated with phage therapy:
staphylococcal skin diseasestaphylococcal skin disease skin infections caused by Pseudomonas Klebsiella Proteus E. coli P. aeruginosa infections in cystic fibrosis patients neonatal sepsisneonatal sepsis surgical wound infections
Likewise, bacteriophage has also been used to treat animal disease.
Bacteriophage:Bacteriophage:Therapeutic UsesTherapeutic Uses
Any Questions?Any Questions?
ReferencesReferences
Brock, T. 1997. Brock, T. 1997. Biology of MicroorganismsBiology of Microorganisms, Prentice Hall, NJ. , Prentice Hall, NJ. Calendar, R. 1988. Calendar, R. 1988. The BacteriophagesThe Bacteriophages, Volume 2, Plenum , Volume 2, Plenum
Press, NY, pp.683-715. Press, NY, pp.683-715. Salyers, A., and D. Whitt. 1994. Salyers, A., and D. Whitt. 1994. Bacterial Pathogenesis: A Bacterial Pathogenesis: A
Molecular ApproachMolecular Approach, ASM Press, Washington D.C. pp.141-, ASM Press, Washington D.C. pp.141-155,169-181. 155,169-181.
Waldor, M. 1998. Bacteriophage biology and bacterial virulence. Waldor, M. 1998. Bacteriophage biology and bacterial virulence. Trends Microbiol. 6:295-296 Trends Microbiol. 6:295-296
Waldor, M., and J. Mekalanos. 1996. Lysogenic conversion by a Waldor, M., and J. Mekalanos. 1996. Lysogenic conversion by a filamentous phage encoding cholera toxin. Science 272:1910-filamentous phage encoding cholera toxin. Science 272:1910-19141914
http://www.evergreen.edu/phage/phagetherapy/phagetherapy.htmhttp://www.evergreen.edu/phage/phagetherapy/phagetherapy.htmllhttp://www.flesheatingbacteria.net/http://www.flesheatingbacteria.net/http://justice.loyola.edu/~klc/BL472/GAS/http://justice.loyola.edu/~klc/BL472/GAS/http://www.med.sc.edu:85/mayer/phage.htmhttp://www.med.sc.edu:85/mayer/phage.htm