2. Bacteriophage (Phage)
โข Definition - Obligate intracellular parasites that
multiply inside bacteria by making use of some or
all of the host biosynthetic machinery
โข Significance
โ Models for animal cell viruses
โ Gene transfer in bacteria
โ Medical applications
โข Identification of bacteria - phage typing
โข Treatment and prophylaxsis???
3. Medical Applications of Phage
โข โI strongly believe phage could become an
effective antibacterial toolโ - Carl Merril, Chief of the
Laboratory of Biochemical Genetics, National Institute of Mental
Health, NIH.
โข โIt might be another string on the bow, such that
when (conventional antibiotics) fail, hereโs
something that has a chance of working. But itโs
not going to be a panaceaโ - 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
โข Exponential Biotherapies (Rockville, MD)
โ Vancomycin resistant Enterococcus facium and Streptococcus
pneumoniae
โข Phage Therapeutics (Bothell, WA)
โ Staphylococcus aureus and Staphylococcus epidermidis
โข Intralytix, Inc. (Baltimore, MD)
โ Salmonella in meat and poultry
โข Biopharm Ltd. (Tblisi, Georgia)
โ Infections associated with burns
โข University of Idaho
โ 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.
8. Types of Bacteriophage
โข 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
โข Eclipse
โ Early genes
โ Phage DNA
synthesis
โ Late genes
โข Intracellular
accumulation
โข Lysis and Release
Total
Phage
Extracellular
Phage
Eclipse
Intracellular
accumulation
phase
Time after Infection
Number
of
Infectious
Particles Lysis
11. Types of Bacteriophage
โข Lysogenic or temperate phage: Phage that
can either multiply via the lytic cycle or
enter a quiescent state in the bacterial cell.
(e.g., ๏ธ)
โ Expression of most phage genes repressed
โ Prophage
โ Lysogen
12. Events Leading to Lysogeny
โข Circularization of the phage chromosome
โ Cohesive ends
Lygase
Closed Circle
Cohesive Ends
Linear Double Stranded Opened Circle
13. Events Leading to Lysogeny
โข Site-specific
recombination
โ Phage coded
enzyme
โข Repression of the
phage genome
โ Repressor protein
โ Specific
โ Immunity to
superinfection
gal bio
gal bio
gal
bio
14. Termination of Lysogeny
โข Induction
โ Adverse conditions
โข Role of proteases
โ recA protein
โ Destruction of
repressor
โข Excision
โข Lytic growth
gal
bio
gal bio
gal bio
gal bio
โข Gene expression
15. Lytic vs Lysogenic Cycle?
โข Role of repressor
โข Role of cro gene product
โข Role of proteases
16. Significance of Lysogeny
โข Model for animal virus transformation
โข Lysogenic or phage conversion
โ Definition: A change in the phenotype of a
bacterial cell as a consequence of lysogeny
โข Modification of Salmonella O antigen
โข Toxin production by Corynebacterium diphtheriae