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: , 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: , 1998.
Phages eyed as agents to protect against harmful E. coli. American Society for Microbiology News 65: , 1999.

5. Bacteriophage T4
Lambda ()

6. Composition and Structure
Nucleic acid
Genome size
Modified bases
Protein
Protection
Infection
Tail
Tail Fibers
Base Plate
Head/Capsid
Contractile Sheath
Structure (T4)
Size
Head or capsid
Tail

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

8. Types of Bacteriophage
Lytic or virulent phage: Phage that can only multiply within bacteria and kill the cell by lysis. (e.g., T4)

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

10. Assay for Lytic Phage Plaque assay Method Plaque forming unit (pfu)
Measures infectious particles
Bacteria
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
gal
bio
Site-specific recombination
Phage coded enzyme
Repression of the phage genome
Repressor protein
Specific
Immunity to superinfection

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

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