Bacteriophage, or phages, are viruses that infect bacteria. They have potential medical applications as alternatives to antibiotics. Some companies are studying phages to treat infections caused by bacteria like Staphylococcus aureus and Salmonella. Phages can either undergo a lytic cycle, where they multiply within the host and cause it to lyse, or a lysogenic cycle where they integrate into the host genome and remain dormant. The lysogenic cycle provides a model for how some animal viruses cause transformation of cells.

1. Bacteriophage

2. Bacteriophage (Phage) Definition - Obligate intracellular parasites that multiply inside bacteria by making use of some or all of the host biosynthetic machinery Significance Models for animal cell viruses Gene transfer in bacteria Medical applications Identification of bacteria - phage typing Treatment and prophylaxsis???

3. Medical Applications of Phage “ I strongly believe phage could become an effective antibacterial tool” - Carl Merril, Chief of the Laboratory of Biochemical Genetics, National Institute of Mental Health, NIH. “ It might be another string on the bow, such that when (conventional antibiotics) fail, here’s something that has a chance of working. But it’s not going to be a panacea” - Joshua Lederberg, Sackler Foundation Scholar at The Rockefeller University Reassessment of Medicinal Phage Spurs Companies to Study Therapeutic Uses American Society for Microbiology News 64:620-623, 1998

4. Medical Applications of Phage Exponential Biotherapies (Rockville, MD) Vancomycin resistant Enterococcus facium and Streptococcus pneumoniae Phage Therapeutics (Bothell, WA) Staphylococcus aureus and Staphylococcus epidermidis Intralytix, Inc. (Baltimore, MD) Salmonella in meat and poultry Biopharm Ltd. (Tblisi, Georgia) Infections associated with burns University of Idaho Escherichia coli O157:H7 in cattle Reassessment of Medicinal Phage Spurs Companies to Study Therapeutic Uses. American Society for Microbiology News 64:620-623, 1998. Phages eyed as agents to protect against harmful E. coli. American Society for Microbiology News 65:666-667, 1999.

5. Bacteriophage T 4 Lambda (  )

6. Composition and Structure Composition Nucleic acid Genome size Modified bases Protein Protection Infection Structure (T 4 ) Size Head or capsid Tail Tail Tail Fibers Base Plate Head/Capsid Contractile Sheath

7. Infection of Host Cells Irreversible attachment Adsorption LPS for T4 Nucleic acid injection Sheath Contraction

8. Types of Bacteriophage Lytic or virulent phage: Phage that can only multiply within bacteria and kill the cell by lysis. ( e.g., T 4 )

9. Lytic Phage Multiplication Cycle Eclipse Early genes Phage DNA synthesis Late genes Intracellular accumulation Lysis and Release Total Phage Extracellular Phage Eclipse Intracellular accumulation phase Time after Infection Number of Infectious Particles Lysis

10. Assay for Lytic Phage Plaque assay Method Plaque forming unit (pfu) Measures infectious particles Bacteria Phage + Phage

11. Types of Bacteriophage Lysogenic or temperate phage: Phage that can either multiply via the lytic cycle or enter a quiescent state in the bacterial cell. ( e.g.,  ) Expression of most phage genes repressed Prophage Lysogen

12. Events Leading to Lysogeny Circularization of the phage chromosome Cohesive ends Lygase Closed Circle Cohesive Ends Linear Double Stranded Opened Circle

13. Events Leading to Lysogeny Site-specific recombination Phage coded enzyme Repression of the phage genome Repressor protein Specific Immunity to superinfection gal bio gal bio gal bio

14. Termination of Lysogeny Induction Adverse conditions Role of proteases recA protein Destruction of repressor Excision Lytic growth Gene expression gal bio gal bio gal bio gal bio

15. Lytic vs Lysogenic Cycle? Role of repressor Role of cro gene product Role of proteases

16. Significance of Lysogeny Model for animal virus transformation Lysogenic or phage conversion Definition: A change in the phenotype of a bacterial cell as a consequence of lysogeny Modification of Salmonella O antigen Toxin production by Corynebacterium diphtheriae