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DEPARTMENT OF MICROBIOLOGY
    FACULTY OF LIFE SCIENCES
      UNIVERSITY OF BENIN
          BENIN CITY.

             COURSE:
MCB 413 (UNDERGRADUATE SEMINAR)

             TOPIC:
         PHAGE THERAPY

           SPEAKER:
PEACE OGHALEOGHENE OKOTIE (MISS)

               MAT. NO:
              LSC0903543

          SUPERVISOR:
       DR A. O. EMOGHENE

                DATE:
        5TH   FEBRUARY, 2013
INTRODUCTION
Phage therapy is a method that involves the
application of specific phages or their products to
human or animal bodies to selectively reduce or
eliminate pathogenic bacteria(Lu and Koeris, 2011).
Although, phage therapy held great promise during
the first half of the 20th century during which it was
used to treat and prevent bacterial infectious diseases
in the former Soviet Union countries and Eastern
Europe, it was abandoned by the West in the 1940s
with the arrival of the antibiotics era.
BACTERIOPHAGES
Bacteriophages are obligate intracellular parasites
 that multiply inside bacteria by making use of some
 or all of the host biosynthetic machinery.

Bacteriophages were jointly discovered by Fredrick
 Twort(1915) and Felix d’Herelle(1917).

d’Herelle coined the term ‘’Bacteriophage’’ signifying
 an entity that eats bacteria and they are so called
 because virulent bacteriophage can cause the
 complete lysis of a susceptible bacterial cell.
Fig 1: The structure of a bacteriophage
                             Source: Carillo and Abendon, 2011.
Plate 1 : An electron micrograph of Vibrio phages

                               Source: Matsuzaki et al., 2005.
PRINCIPLES OF PHAGE BIOLOGY IN
             THERAPY
Phages are classified into 2 based on their life cycle:
Lytic phages
Lysogenic phages

Lytic phages are thought to be more suitable therapeutic
candidates because:
some lysogenic phages have toxic genes in their genome.
lysogenic     phages     can    create   phage-resistant
bacteria(Skurnik and Strauch, 2006).

The ability of the phage to kill the bacterial cell at the end
of the infectious cycle is the cornerstone of the idea of
phage therapy.
Fig 2: Schematic illustration of phage-induced bacteriolysis
                                Source: Matsuzaki et al., 2005.
Phases of the lytic bacteriophage
              cycle
1. Adsorption.
2. Injection of nucleic acid.
3. Expression of phage early proteins.
4. Replication of phage genome.
5. Expression of phage late proteins.
6. Assembling of phage heads and tails and packaging
   of phage genome.
7. Lysis of host bacterium to release the new phage
   progeny.
                                        Ryan et al., 2011.
Table 1: Some examples of phages and the bacterial hosts they are used against.




                                               Source: Hermoso et al., 2007.
ROUTES OF ADMINISTRATION OF PHAGES
Orally by drinking or swallowing of tablets

Aerosols

Topical application to lesions or infected wounds

Injections are rarely used so as to avoid the risk of
chemical contaminants and prevent the phage from
getting confronted by the immune system which
naturally fights against viruses introduced into the
blood stream.
Some diseases treated with
          phage therapy
Pyrogenic inflammatory disease of Staphylococcus
 aureus which is treated using ΦMR11.

Septicemia which is caused by Vibro vulnificus and is
 treated using phage CK2.

Dysentery caused by Escherichia coli and is treated
 using T4 bacteriophage.
PHAGE PRODUCTS used IN PHAGE
            THERAPY
Living phages

Non-replicating genetically modified phages

Phage lysin

Phage holin

Protein antibiotics

Vaccines
                                Hermoso et al., 2007.
ADVANTAGES OF PHAGE THERAPY OVER
        CHEMOTHERAPY
 Phage therapy is effective against multidrug -resistant
  pathogenic bacteria.
 It has high specificity for target bacteria.
 It can rapidly respond to the appearance of phage
  resistant mutants.
 The cost of developing a phage system is cheaper than
  that of developing a new antibiotic.
 Unlike chemotherapy, side effects are usually
  uncommon because phages or their products do not
  affect eukaryotic cells.
                                Source: Matsuzaki et al.,2005.
PROBLEMS TO OVERCOME
Inactivation of administered phages or lysin by a
 neutralizing antibody and allergic reactions to them.

Appearance of mutants resistant to phages.


Capture and transfer of bacterial toxin genes by
 phages.
POSSIBLE SOLUTIONS TO PROBLEMS
The hazards may be mitigated by employing phage
therapeutics:
with narrow host ranges.
that are unable to display lysogeny.
that do not carry toxin genes.
that display minimal tendency towards DNA
  transduction between bacteria.
which are purified away from bacterial toxins.
conclusion
The worldwide increase of pathogenic bacteria
resistant to antibiotics makes it an imperative to
exploit alternative strategies to combat this
threat. Appropriately administered phage
therapy is very effective against these
multidrug-resistant bacteria.
Although some problems remain to be
solved, many scientists are of the opinion that
phage therapy will find a niche in modern
Western medicine in the future.
Thank
 you

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Phage Therapy Against Multidrug-Resistant Bacteria

  • 1. DEPARTMENT OF MICROBIOLOGY FACULTY OF LIFE SCIENCES UNIVERSITY OF BENIN BENIN CITY. COURSE: MCB 413 (UNDERGRADUATE SEMINAR) TOPIC: PHAGE THERAPY SPEAKER: PEACE OGHALEOGHENE OKOTIE (MISS) MAT. NO: LSC0903543 SUPERVISOR: DR A. O. EMOGHENE DATE: 5TH FEBRUARY, 2013
  • 2. INTRODUCTION Phage therapy is a method that involves the application of specific phages or their products to human or animal bodies to selectively reduce or eliminate pathogenic bacteria(Lu and Koeris, 2011). Although, phage therapy held great promise during the first half of the 20th century during which it was used to treat and prevent bacterial infectious diseases in the former Soviet Union countries and Eastern Europe, it was abandoned by the West in the 1940s with the arrival of the antibiotics era.
  • 3. BACTERIOPHAGES Bacteriophages are obligate intracellular parasites that multiply inside bacteria by making use of some or all of the host biosynthetic machinery. Bacteriophages were jointly discovered by Fredrick Twort(1915) and Felix d’Herelle(1917). d’Herelle coined the term ‘’Bacteriophage’’ signifying an entity that eats bacteria and they are so called because virulent bacteriophage can cause the complete lysis of a susceptible bacterial cell.
  • 4. Fig 1: The structure of a bacteriophage Source: Carillo and Abendon, 2011.
  • 5. Plate 1 : An electron micrograph of Vibrio phages Source: Matsuzaki et al., 2005.
  • 6. PRINCIPLES OF PHAGE BIOLOGY IN THERAPY Phages are classified into 2 based on their life cycle: Lytic phages Lysogenic phages Lytic phages are thought to be more suitable therapeutic candidates because: some lysogenic phages have toxic genes in their genome. lysogenic phages can create phage-resistant bacteria(Skurnik and Strauch, 2006). The ability of the phage to kill the bacterial cell at the end of the infectious cycle is the cornerstone of the idea of phage therapy.
  • 7. Fig 2: Schematic illustration of phage-induced bacteriolysis Source: Matsuzaki et al., 2005.
  • 8. Phases of the lytic bacteriophage cycle 1. Adsorption. 2. Injection of nucleic acid. 3. Expression of phage early proteins. 4. Replication of phage genome. 5. Expression of phage late proteins. 6. Assembling of phage heads and tails and packaging of phage genome. 7. Lysis of host bacterium to release the new phage progeny. Ryan et al., 2011.
  • 9. Table 1: Some examples of phages and the bacterial hosts they are used against. Source: Hermoso et al., 2007.
  • 10. ROUTES OF ADMINISTRATION OF PHAGES Orally by drinking or swallowing of tablets Aerosols Topical application to lesions or infected wounds Injections are rarely used so as to avoid the risk of chemical contaminants and prevent the phage from getting confronted by the immune system which naturally fights against viruses introduced into the blood stream.
  • 11. Some diseases treated with phage therapy Pyrogenic inflammatory disease of Staphylococcus aureus which is treated using ΦMR11. Septicemia which is caused by Vibro vulnificus and is treated using phage CK2. Dysentery caused by Escherichia coli and is treated using T4 bacteriophage.
  • 12. PHAGE PRODUCTS used IN PHAGE THERAPY Living phages Non-replicating genetically modified phages Phage lysin Phage holin Protein antibiotics Vaccines Hermoso et al., 2007.
  • 13. ADVANTAGES OF PHAGE THERAPY OVER CHEMOTHERAPY Phage therapy is effective against multidrug -resistant pathogenic bacteria. It has high specificity for target bacteria. It can rapidly respond to the appearance of phage resistant mutants. The cost of developing a phage system is cheaper than that of developing a new antibiotic. Unlike chemotherapy, side effects are usually uncommon because phages or their products do not affect eukaryotic cells. Source: Matsuzaki et al.,2005.
  • 14. PROBLEMS TO OVERCOME Inactivation of administered phages or lysin by a neutralizing antibody and allergic reactions to them. Appearance of mutants resistant to phages. Capture and transfer of bacterial toxin genes by phages.
  • 15. POSSIBLE SOLUTIONS TO PROBLEMS The hazards may be mitigated by employing phage therapeutics: with narrow host ranges. that are unable to display lysogeny. that do not carry toxin genes. that display minimal tendency towards DNA transduction between bacteria. which are purified away from bacterial toxins.
  • 16. conclusion The worldwide increase of pathogenic bacteria resistant to antibiotics makes it an imperative to exploit alternative strategies to combat this threat. Appropriately administered phage therapy is very effective against these multidrug-resistant bacteria. Although some problems remain to be solved, many scientists are of the opinion that phage therapy will find a niche in modern Western medicine in the future.