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Phage therapy
- 1. PHAGE THERAPY AN ALTERNATIVE TO ANTIBIOTICS IN THE AGE OF MULTI DRUG RESISTANCE MUHAMMAD IQBAL M.PHIL. MICROBIOLOGY 2ND SEMESTER 2014-GCUF-03745
- 2. Contents Introduction to Antibiotic Resistance Phage Therapy Introduction History Prep of phage Mechanism of Action Examples Phage vs Antibiotics Challenges
- 3. Antibiotics Resistance The ability of bacteria and other microorganisms to resist the effects of an antibiotic to which they were once sensitive. Antibiotics resistance is mostly developed due to Use and misuse of antibiotics Genetic variations and mutations in bacteria causing disease.(Gulberg E et al.,2011)
- 5. Bacteriophage viruses that only infect bacteria and attack only a single bacterial strains. This specificity together with the killing capacity makes them the natural enemies of bacteria
- 6. Life cycle of bacteriophage
- 7. Phage therapy Use of bacteriophage to treat pathogenic bacterial infection Using phages or their products as bio- agents for the treatment or prophylaxis of bacterial infectious disease
- 8. History French Canadian microbiologist Felix d’Herelle, first observed in 1910 the bacteriophage phenomenon In 1917 he began testing his phages in human patients administration them to a 12 year old boy with severe dysentery resulting in complete recovery.
- 9. Cont.… First administration of phages was given in 1921 at the hospital in Paris. In 1945 Phage therapy was abandoned in the Western world, but maintained on a large scale in Poland and the USSR where infections continued being successfully treated.(Derek et al .2017)
- 10. Historical Medical Uses of Phage Therapy Anthrax Cholera Dysentry Gonorrhea Meningitis Tuberculosis Typhoid fever etc….. (Xavier et al .,2014)
- 11. Where we can find Phages? In Human and Animals Intestine In Running Water In the soil Sewage from corpses
- 14. Spot test Middle broke top Agar (jiffy et al., 2015)
- 15. Mode of action Lytic Cycle
- 16. Engineered nonlytic antibacterial phage Temperate phage engineered to deliver synthetic gene network undergo a latent lifecycle after infection, called lysogeny. Here, the viral genome integrates into the bacterium's chromosome as a prophage. where it can express antimicrobial proteins (AMPs) that interfere with intracellular processes and cause bacterial death .
- 17. Cont….. Phagemids can also deliver synthetic gene network on a synthetic plasmid that encode for antibacterial proteins, such encoding a RNA- guided CRISPR-associated (Cas) nucleases for sequence-specific nonlytic bacterial death and plasmid removal. Phagemid plasmids can also encode for AMPs (Thiel et al.,2004).
- 19. Killing of Mycobacterium avium and M.tuberculosis by a Mycobacteriophage Delivered by a Nonvirulent Mycobacterium Tuberculosis is a serious public health problem that results in millions of deaths around the world each year Mycobacterium smegmatis, an avirulent mycobacterium, is used to deliver the lytic phage TM4 where both M. avium and M. tuberculosis reside within macrophages
- 20. These results showed that treatment of M. avium– infected, as well as M. tuberculosis infected, RAW 264.7 macrophages, with M. smegmatis transiently infected with TM4, resulted in a significant time and titer-dependent reduction in the number of viable intracellular bacilli( Lia et al.,2006).
- 22. Experimental phage therapy against S.aureus in mice This study describes a bacteriophage active against Staphylococcus aureus, including methicillin-resistant staphylococcal strains. When inoculated into mice simultaneously with S. aureus (108 CFU/mouse), then 97% of the mice recovered(Koen et al., 2015).
- 24. Current status of human phage therapy Still phage therapy Approved in Russia Poland Georgia
- 25. Bacteriophage vs Antibiotics Very specific Abundant in environment no side effects have been reported Replicate at the site of infection Good alternative for patients allergic to antibodies Their action is bactericidal Target normal flora and pathogens Have sever side effects like allergies and secondary infection Have sever side effects like allergies and secondary infection If patient is allergic to antibiotic, treatment is very difficult Some are bacteriostatic
- 26. Challenges Host Range Bacterial Debries present in the phage preparation Antiphage Antibodies
- 27. References Broxmeyer L et al Killing of Mycobacterium avium and Mycobacterium tuberculosis by a Mycobacteriophage Delivered by a Nonvirulent Mycobacterium: AModel for Phage Therapy of Intracellular Bacterial Pathogens J Infect Dis 186: 1155-60 Brussow H (2005) Phage therapy: the Escherichia coli experience Microbiol 151:2133-40 Carlton R M (1999) Phage therapy: Past history and Future prospects Arch Immunol Ther Exp 47: 267-74 Haq I U et al (2012) Bacteriophages and their Implications on Future Biotechnology:A Review J Virol 9. Inal J M (2003) Phage Therapy: a Reappraisal of Bacteriophages as Antibiotics Arch Immunol Ther Exp 51:237-44
- 28. Cont….. Skurnik M and Strauch E (2006) Phage therapy: Facts and Fiction Int J Med Microbiol 296 :5-14 Sulakvelidze A (2011) The Challenges of Bacteriophage Therapy Eur I Pharm 10:14-18 Thiel K (2004) Old dogma, new tricks—21st Century phage therapy Nat Biotechnol 22:31-36