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
INTRODUCTIONPhage therapy is a method that involves theapplication of specific phages or their products tohuman or animal bodies to selectively reduce oreliminate pathogenic bacteria(Lu and Koeris, 2011).Although, phage therapy held great promise duringthe first half of the 20th century during which it wasused to treat and prevent bacterial infectious diseasesin the former Soviet Union countries and EasternEurope, it was abandoned by the West in the 1940swith the arrival of the antibiotics era.
BACTERIOPHAGESBacteriophages 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 THERAPYPhages are classified into 2 based on their life cycle:Lytic phagesLysogenic phagesLytic phages are thought to be more suitable therapeuticcandidates because:some lysogenic phages have toxic genes in their genome.lysogenic phages can create phage-resistantbacteria(Skurnik and Strauch, 2006).The ability of the phage to kill the bacterial cell at the endof the infectious cycle is the cornerstone of the idea ofphage therapy.
Fig 2: Schematic illustration of phage-induced bacteriolysis Source: Matsuzaki et al., 2005.
Phases of the lytic bacteriophage cycle1. 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 PHAGESOrally by drinking or swallowing of tabletsAerosolsTopical application to lesions or infected woundsInjections are rarely used so as to avoid the risk ofchemical contaminants and prevent the phage fromgetting confronted by the immune system whichnaturally fights against viruses introduced into theblood stream.
Some diseases treated with phage therapyPyrogenic 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 THERAPYLiving phagesNon-replicating genetically modified phagesPhage lysinPhage holinProtein antibioticsVaccines 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 OVERCOMEInactivation 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 PROBLEMSThe hazards may be mitigated by employing phagetherapeutics: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 bacteriaresistant to antibiotics makes it an imperative toexploit alternative strategies to combat thisthreat. Appropriately administered phagetherapy is very effective against thesemultidrug-resistant bacteria.Although some problems remain to besolved, many scientists are of the opinion thatphage therapy will find a niche in modernWestern medicine in the future.