بسم الله الرحمن الرحيم: بسم الله الرحمن الرحيم Phage Therapy: Phage Therapy Fatma F. Abu-Qados To: Dr.Abdelraouf A. El-Manama 30.01.11 What is Phage?: What is Phage? “ Viruses that parasite on bacteria “ Distinct from the animal and plant viruses. Simple and abundant organisms on earth. Have either a “lytic” or a “lysogenic” life cycle. Slide 4: Hello .. I’m Phage Types of Phages : Types of Phages λ phage – Lysogen T2 phage T4 phage T7 phage M13 phage MS2 phage P1 phage Enterobacteria phage P2 What is Phage Therapy ?: What is Phage Therapy ? IS the therapeutic use of bacteriophages to treat pathogenic bacterial infections. But .. biocontrol : If target host of treatment is not an animal Lytic Vs. Lysogenic: Lytic Vs. Lysogenic Destruction (lysis ) Growth suppression effects (lysogeny) lytic phages are the most suitable candidates for phage therapy.. Why ?? because they quickly reproduce within and lyse the bacteria in their host range, growing exponentially in number. In contrast , temperate phages ( lysogenic) , which can bolster their bacterial host's virulence , resilience , and general capacity to proliferate are generally unsuitable for therapeutic applications. Lytic cycle ..: Lytic cycle .. Attachment: Attachment More & More: More & More Penetration & swelling: Penetration & swelling Lyses: Lyses Spreading: Spreading Amplfication ..: Depending on the species and conditions , each “parent” phage can produce on average approximately 200 “daughters” per lytic cycle. 40 000 progeny at the end of the 2nd cycle; 8 million at the end of the 3rd cycle; 1.6 billion at the end of the 4th cycle; and so on…. Amplfication .. History: Since ancient times, river waters having the ability to cure infectious diseases, such as leprosy . Phages were discovered in 1915 by British microbiologist Felix Twort , and, independently in 1917, by French-Canadian microbiologist Felix d’Hérelle. Twort did not pursue his discovery, whereas d’Hérelle systematically investigated the nature of bacteriophages and explored their ability to function as therapeutic agents History Is that still being Used now ?: Is that still being Used now ? Although extensively used and developed mainly in former Soviet Union countries for about 90 years, this method of therapy is still being tested elsewhere for treatment of a variety of bacterial and poly-microbial biofilm infections , and has not yet been approved in countries other than Georgia. Advantages: Advantages Phages thrive in the presence of bacteria, and die out in their absence. Extreme specificity and chemically large nature. Do not cause allergies or affect the body's natural immune system . Low chemotherapeutic index . Support and enhance vital microflora. Cont. Adv.: Cont. Adv. More rapidly and effectively than standard antibiotics. Have a long shelf life (up to 2 years). Production costs of phages are low . "green-natural-alternative" and its production is environment-friendly. For both prevention & treatment . Administered in a limited number of small doses over a short period of time. Disadvantages : Disadvantages Must be refrigerated until used . High specificity …. when the exact species of an infecting bacteria is unknown or if there is a multiple infection . Should be tested in the lab prior to application, making phages less suitable for acute cases where time is not available. Cont. Disadv.: Cont. Disadv. Resistance However, evolution drives the rapid emergence of new phages that can destroy bacteria that have become resistant. This means that there should be an "inexhaustible" supply. Injected into the bloodstream are recognized by the human immune system . For this reason, it appears that a particular phage can only be used once for intravenous treatment Where we can find Phage?: Where we can find Phage? In humans and animal intestines In running water In the soil Effluent outlets , sewage From corpses . Culture: Culture Because Phages are "bacterium-specific" , it is necessary to take a swab from the patient and culture it prior to treatment. The samples are taken and applied to the bacteria that are to be destroyed (To be tested) which have been cultured on growth medium. If the bacteria die, as usually happens, the mixture is centrifuged ; the phages collect on the top of the mixture and can be drawn off. Occasionally, isolation of therapeutic phages can require a few months to complete, but clinics generally keep supplies of phage cocktails for the most common bacterial strains in a geographical area. How can be Administrated ? : How can be Administrated ? Orally.. Topically on infected wounds Injection is rarely used, avoiding immune system stimulation.. Topical use ..: Topical use .. Treatment 4 WHAT ?: Treatment 4 WHAT ? For bacterial infections .. e.g : laryngitis, skin infections, dysentery, conjunctivitis, periodontitis, gingivitis, sinusitis, urinary tract infections and intestinal infections, burns, boils,poly-microbial biofilms on chronic wounds, ulcers and infected surgical sites. Other uses ..: Other uses .. Veterinary science Agriculture Food additive . phages against Listeria on cheese and meat are generally recognized as safe (GRAS status). Phage on Wounds: Phage on Wounds Future hopes: Future hopes Cancer therapy …. ! Meningitis ,,, cross the BBB …! Conclusion: Conclusion Multidrug-resistant bacteria have opened a second window for phage therapy. Phage therapy can then serve as a stand-alone therapy for infections that are fully resistant . It will also then be able to serve as a co-therapeutic agent for infections that are still susceptible to antibiotics. Slide 35: Questions ?