The document summarizes a presentation on phage therapy given by Peace Oghalohene Okotie. It discusses how bacteriophages were discovered and can be used to selectively target and lyse pathogenic bacteria. Phage therapy involves using lytic bacteriophages or their products to treat bacterial infections. It describes the lytic bacteriophage lifecycle and how routes of administration avoid the immune system. While phage therapy was widely used in the early 20th century, antibiotics replaced it. However, with increasing antibiotic resistance, phage therapy is being reexamined as an alternative to treat multidrug-resistant bacteria. The document outlines some challenges but also potential solutions to issues like host resistance.
Beyond the EU: DORA and NIS 2 Directive's Global Impact
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.