Phage therapy

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Phage therapy

  1. 1. بسم الله الرحمن الرحيم
  2. 2. Phage Therapy Fatma F. Abu-Qados To: Dr.Abdelraouf A. El-Manama 30.01.11
  3. 3. What is Phage? <ul><li>“ Viruses that parasite on bacteria “ </li></ul><ul><li>Distinct from the animal and plant viruses </li></ul><ul><li>Simple and abundant organisms on earth. </li></ul><ul><li>Have either a “lytic” or a “lysogenic” life cycle. </li></ul>
  4. 4. Hello .. I’m Phage
  5. 5. Types of Phages <ul><li>λ phage – Lysogen </li></ul><ul><li>T2 phage </li></ul><ul><li>T4 phage </li></ul><ul><li>T7 phage </li></ul><ul><li>M13 phage </li></ul><ul><li>MS2 phage </li></ul><ul><li>P1 phage </li></ul><ul><li>Enterobacteria phage P2 </li></ul>
  6. 6. What is Phage Therapy ? <ul><li>IS the therapeutic use of bacteriophages to treat pathogenic bacterial infections. </li></ul><ul><li>But .. &quot; biocontrol “ : </li></ul><ul><li>If target host of treatment is not an animal </li></ul>
  7. 7. Lytic Vs. Lysogenic <ul><li>Destruction (lysis ) </li></ul><ul><li>Growth suppression effects (lysogeny) </li></ul><ul><li>lytic phages are the most suitable candidates for phage therapy.. </li></ul><ul><li>Why ?? because they quickly reproduce within and lyse the bacteria in their host range, growing exponentially in number. </li></ul><ul><li>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.  </li></ul>
  8. 8. Lytic cycle …
  9. 9. Attachment
  10. 10. More & More
  11. 11. Penetration & swelling
  12. 12. Lyses
  13. 13. Spreading
  14. 15. <ul><li>Depending on the species and conditions , each “parent” phage can produce on average approximately 200 “daughters” per lytic cycle. </li></ul><ul><li>40 000 progeny at the end of the 2nd cycle; </li></ul><ul><li>8 million at the end of the 3rd cycle; </li></ul><ul><li>1.6 billion at the end of the 4th cycle; </li></ul><ul><li>and so on…. </li></ul>Amplfication ..
  15. 16. <ul><li>Since ancient times, river waters having the ability to cure infectious diseases, such as leprosy . </li></ul><ul><li>Phages were discovered in 1915 by British microbiologist Felix Twort , and, independently in 1917, by French-Canadian microbiologist Felix d’Hérelle. </li></ul><ul><li>Twort did not pursue his discovery, whereas d’Hérelle systematically investigated the nature of bacteriophages and explored their ability to function as therapeutic agents </li></ul>History
  16. 17. Is that still being Used now ? <ul><li>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. </li></ul>
  17. 18. Advantages <ul><li>Phages thrive in the presence of bacteria, and die out in their absence. </li></ul><ul><li>Extreme specificity and chemically large nature. </li></ul><ul><li>Do not cause allergies or affect the body's natural immune system . </li></ul><ul><li>Low chemotherapeutic index . </li></ul><ul><li>Support and enhance vital microflora. </li></ul>
  18. 19. Cont. Adv. <ul><li>More rapidly and effectively than standard antibiotics. </li></ul><ul><li>Have a long shelf life (up to 2 years). </li></ul><ul><li>Production costs of phages are low . </li></ul><ul><li>&quot;green-natural-alternative&quot; and its production is environment-friendly. </li></ul><ul><li>For both prevention & treatment . </li></ul><ul><li>Administered in a limited number of small doses over a short period of time. </li></ul>
  19. 20. Disadvantages <ul><li>Must be refrigerated until used . </li></ul><ul><li>High specificity …. when the exact species of an infecting bacteria is unknown or if there is a multiple infection . </li></ul><ul><li>Should be tested in the lab prior to application, making phages less suitable for acute cases where time is not available. </li></ul>
  20. 21. Cont. Disadv. <ul><li>Resistance </li></ul><ul><li>However, evolution drives the rapid emergence of new phages that can destroy bacteria that have become resistant. This means that there should be an &quot;inexhaustible&quot; supply. </li></ul><ul><li>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 </li></ul>
  21. 22. Where we can find Phage? <ul><li>In humans and animal intestines </li></ul><ul><li>In running water </li></ul><ul><li>In the soil </li></ul><ul><li>Effluent outlets , sewage </li></ul><ul><li>From corpses . </li></ul>
  22. 23. Culture <ul><li>Because Phages are &quot;bacterium-specific&quot; , it is necessary to take a swab from the patient and culture it prior to treatment. </li></ul><ul><li>The samples are taken and applied to the bacteria that are to be destroyed (To be tested) which have been cultured on growth medium. </li></ul><ul><li>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. </li></ul><ul><li>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. </li></ul>
  23. 25. How can be Administrated ? <ul><li>Orally.. </li></ul><ul><li>Topically on infected wounds </li></ul><ul><li>Injection is rarely used, avoiding immune system stimulation.. </li></ul>
  24. 26. Topical use ..
  25. 27. Treatment 4 WHAT ? <ul><li>For bacterial infections .. </li></ul><ul><li>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. </li></ul>
  26. 28. Other uses .. <ul><li>Veterinary science </li></ul><ul><li>Agriculture </li></ul><ul><li>Food additive . </li></ul><ul><li>phages against Listeria on cheese and meat are generally recognized as safe (GRAS status). </li></ul>
  27. 29. Phage on Wounds
  28. 33. Future hopes <ul><li>Cancer therapy …. ! </li></ul><ul><li>Meningitis ,,, cross the BBB …! </li></ul>
  29. 34. Conclusion <ul><li>Multidrug-resistant bacteria have opened a second window for phage therapy. </li></ul><ul><li>Phage therapy can then serve as a stand-alone therapy for infections that are fully resistant . </li></ul><ul><li>It will also then be able to serve as a co-therapeutic agent for infections that are still susceptible to antibiotics. </li></ul>
  30. 35. Questions ?

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