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.

Source: Hermoso et al., 2007.

Table 1: Some examples of phages and the bacterial hosts they are used against.

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 CHEMOTHERAPYPhage 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.

conclusionThe 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