Download BACTERIOPHAGE

BACTERIOPHAGE
• Are viruses which attack the bacteria.
• Are highly host specific.
• Are classified according to the bacteria they infect, e.g.
typhoid phages, staphylococcus phages……etc.
MORPHOLOGY:
Head: polyhedral (icosahedral) in shape packing NA.
Tail: is contracle and consists of parts
(a) Hollow core.
(b) Contractile sheath.
(c) Terminal base-plate to which is attached fibers.
Bacteriophage Replication:
.Adsorption : occurs with the tail fibers.
.Penetration : the contractile sheath behave as hypodermic
syringes injecting phage NA into the bacterial cell wall.
.Eclipse phase : occurs in two stages,
a) Early transcription and translation leads to early protein
formation ( polymerase and other enzymes)
b) Late transcription leads to protein formation (structural
protein), and phage NA formation.
.Assembly : Is the irreversible combination of phage NA with
protein coat.
.Lysis and liberation of new phage : the cell bursts and
liberates the newly formed phages.
When a phage infects bacteria it results in either:
) A normal lytic cycle.
) A lysogenic cycle, in which the viral DNA is inserted into
the bacterial chromosome to form a prophage and
result in a lysogenic bacterial cell.
Very rarely a prophage is spontaneously induced to
form a vegetative phage and result in lytic cycle. UV
light, X-ray, N. mustard, etc….increase the frequency of
this event.
Effect on the genome of the bacterial cell:
.Lysogenic conversion: acquisition of new cell properties as a
result of phage infection e.g. C. diphtheria and Staph aureus
produce strong toxin only when lysogenized by phage.
.Transduction: bacteriophages mediate genetic transfer
between bacteria.
HOST RESPONSE TO VIRAL INFECTION
• Humoral immune response:
Antibody response to neutralize and eliminate the
ongoing Infection and can also prevent reinfection.
• Cell mediated immune response:
Stimulate the production of lymphokines as
Interferons which is very important for defense
against viruses.
INTERFERON
Are produced by cells in response to viral infection.
Properties:
) Are the first line of body defense against viral infection.
&) Are host coded protein.
') It inhibits viral replication.
() Host species specific.
)) Not viral specific.
*) There are IFN-α, IFN-β, and IFN-γ.
+) It acts also as cell regulatory activity ( activation of natural
killer cells, activation of monocytes and macrophages and
inhibition of cell growth.
,) Recombinant DNA techniques now allow production of
inexpensive large amount of interferon by yeast and
bacteria.
CLINICAL USES:
• Used in treatment of severe viral infection e.g. rabies,
herpetic encephalitis,….etc
• In the treatment of persistent viral infections e.g.
hepatitis B & C,…etc
• Used as anticancer agent on the basis of their cell
regulation and immunomodulation properties.
• Treatment of multiple sclerosis.
ANTIVIRAL CHEMOTHERAPY
Because viruses are intracellular parasite, an antiviral agent
must be capable of selectively inhibiting viral functions
without damaging the host cell.
A. Nucleoside analogues:
They inhibit viral replication by inhibiting
polymerases for nucleic acid replication.
0. Acyclovir:
Is antiherpetic drug (guanosine analogue).
it must be phosphorylated to be active and this
occurs by the herpes virus-encoded thymidine
kinase enzyme and hence the drug is only active
in infected cells. The drug is available as topical,
oral and parentral.
&. Gancyclovir:
Is related to acyclovir used for the treatment
of CMV in immunocompromised patients e.g.
Renal transplant patient and in AIDS patients.
'. Foscarnet :
Is given in resistant cases of herpes and CMV
infections and does not need phosphorylation.
(.Reversed transcriptase inhibitors:
Used mainly for the treatment of AIDS
a) Zidovudin (ZDV)
b) Didanosine (ddi) dideoxyinosine.
c) Zalcitabine (ddC) dideoxycytidine.
d) Stavudine (D<T).
e) Lamivudine which is also used in hepatitis B
infection.
).Ribavirin:
For the treatment of RSV and influenza
infection in infants. In HCV infections combined
with interferon.
B. Nucleotide analogues:
Cidofovir is the first member of this new class
which differ from the nucleoside analogue in
having an attached phosphate group. It is active
against CMV, HSV, and papilloma virus.
C. Protease inhibitors:
Viral protease enzyme is present in the late stage of
replication of HIV.
0.Saquinavir is the first protease inhibitor for the
treatment of AIDS.
&. Indinavir & Ritonavir are used in combination
with reversed transcriptase inhibitor for AIDS.
D.Fusion inhibitor:
Fuzeon is peptide that blocks the virus and cellular
membrane fusion step in entry of HIV into cells.
E.Anti-influenza drugs:
0) Amantadin and Rimantadine:
Inhibit Influenza A virus by blocking viral
uncoating.
&)Neuraminidase inhibitor:
Tamiflu and Zanamivir are effective against
avian flue.