Bacteriophage (page 2)
(This chapter has 2 pages)
© Kenneth Todar, PhD
Lysogenic Infections
Bacteriophage
Lambda, the lysogenic phage that infects E. coli. Bock laboratories.
University of Wisconsin-Madison.
Lysogenic or temperate infection rarely results in lysis of the
bacterial host cell. Lysogenic viruses, such as lambda which
infects E. coli, have a
different strategy than lytic viruses for their
replication. After penetration, the virus DNA integrates
into the bacterial chromosome and it becomes replicated every
time the cell duplicates its chromosomal DNA during normal cell
division. The life cycle of a lysogenic bacteriophage is illustrated
below.
The
lysogenic cycle of a temperate bacteriophage such as lambda.
Temperate viruses usually do not kill the host bacterial cells they
infect. Their chromosome becomes integrated into a specific section of
the host cell chromosome. Such phage DNA is called prophage and the host bacteria are
said to be lysogenized. In the
prophage state all the
phage genes except one are repressed. None of the usual early proteins
or structural proteins are formed.
The phage gene that is expressed is an important one because it codes
for the synthesis of a repressor
molecule that prevents the synthesis
of phage enzymes and proteins required for the lytic cycle. If the
synthesis
of the repressor molecule stops or if the repressor becomes
inactivated,
an enzyme encoded by the prophage is synthesized which excises the
viral DNA from the bacterial chromosome. This excised DNA (the phage
genome) can now behave like a lytic virus, that is to produce new viral
particles and eventually lyse the host cell (see diagram above). This
spontaneous derepression is a
rare event occurring about one in 10,000
divisions of a lysogenic bacterium., but it assures that new phage are
formed which can proceed to infect other cells.
Usually it is difficult to recognize lysogenic bacteria because
lysogenic and nonlysogenic cells appear identical. But in a few
situations, the prophage supplies genetic information such that the
lysogenic bacteria exhibit a new characteristic (new phenotype),
not displayed by the nonlysogenic cell, a phenomenon
called lysogenic conversion.
Lysogenic conversion has some
interesting manifestations in pathogenic bacteria that only exert
certain determinants of virulence when they are in a lysogenized state.
Hence, Corynebacterium
diphtheriae can only produce the toxin
responsible for the disease if it carries a temperate virus called
phage beta. Only lysogenized streptococci produce the
erythrogenic
toxin (pyrogenic exotoxin) which causes the skin rash of scarlet fever;
and some botulinum toxins are synthesized only by lysogenized
strains of C. botulinum.
Corynebacterium
diphtheriae only produces
diphtheria toxin
when lysogenized by beta phage.C.
diphtheriae strains that
lack the prophage do not produce diphtheria toxin and do not cause the
disease diphtheria. Surprisingly, the genetic information for
production
of the toxin is found to be on the phage chromosome, rather than
the bacterial chromosome.
A similar phenomenon to lysogenic conversion exists in the relationship
between an animal tumor virus and its host cell. In both instances,
viral
DNA is incorporated into the host cell genome, and there is a
coincidental
change in the phenotype of the cell. Some human cancers may be caused
by viruses which establish a state in human cells analogous to lysogeny
in bacteria.
Phage Therapy
Phage therapy is the therapeutic use of lytic bacteriophages to treat
pathogenic bacterial infections. Phage therapy is an alternative to
antibiotics being developed for clinical use by research groups in
Eastern Europe and the U.S. After having been extensively used and
developed mainly in former Soviet Union countries for about 90 years,
phage therapies for a variety of bacterial and poly microbial
infections are now becoming available on an experimental basis in other
countries, including the U.S. The principles of phage therapy have
potential applications not only in human medicine, but also in
dentistry, veterinary science, food science and agriculture.
An important benefit of phage therapy is derived from the observation
that bacteriophages are much more specific than most antibiotics that
are in clinical use. Theoretically, phage therapy is harmless to the
eucaryotic host undergoing therapy, and it should not affect the
beneficial normal flora of the host. Phage therapy also has few, if
any, side effects, as opposed to drugs, and does not stress the liver.
Since phages are self-replicating in their target bacterial cell, a
single, small dose is theoretically efficacious. On the other hand,
this specificity may also be disadvantageous because a specific phage
will only kill a bacterium if it is a match to the specific subspecies.
Thus, phage mixtures may be applied to improve the chances of success,
or clinical samples can be taken and an appropriate phage identified
and grown.
Phages are currently being used therapeutically to treat bacterial
infections that do not respond to conventional antibiotics,
particularly in the country of Georgia. They are reported to be
especially successful where bacteria have constructed a biofilm
composed of a polysaccharide matrix that antibiotics cannot penetrate.
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