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