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Bacteriophages

A bacteriophage is a type of virus that infects bacteria. In fact, the word "bacteriophage" literally
means "bacteria eater," because bacteriophages destroy their host cells. Types of bacteriophages
are:- Enterobacter phage, M13 bacteriophage, Phi X 174, Bacteriophage MS2, Plasmaviridae,
Bacillus phage phi29, fusseloviridae, Ampullaviridae. Bacteriophages are much more specific
than antibiotics. They are typically harmless not only to the host organism, but also to other
beneficial bacteria, such as the gut flora, reducing the chances of opportunistic infections. They
have a high therapeutic index, that is, phage therapy would be expected to give rise to few side
effects. Because phages replicate in vivo (in cells of living organism), a smaller effective dose
can be used. On the other hand, this specificity is also a disadvantage: a phage will only kill a
bacterium if it is a match to the specific strain. Consequently, phage mixtures are often applied to
improve the chances of success, or samples can be taken and appropriate phages identified and
grown. Bacteriophage treatment offers a possible alternative to conventional antibiotic
treatments for bacterial infection.[32] It is conceivable that, although bacteria can develop
resistance to phage, the resistance might be easier to overcome than resistance to
antibiotics.[33][34] Just as bacteria can evolve resistance, viruses can evolve to overcome
resistance.[35]

Bacteriophages are very specific, targeting only one or a few strains of bacteria. Traditional
antibiotics have more wide-ranging effect, killing both harmful bacteria and useful bacteria such
as those facilitating food digestion. The species and strain specificity of bacteriophages makes it
unlikely that harmless or useful bacteria will be killed when fighting an infection.

A few research groups in the West are engineering a broader spectrum phage, and also a variety
of forms of MRSA treatments, including impregnated wound dressings, preventative treatment
for burn victims, phage-impregnated sutures. Enzybiotics are a new development at Rockefeller
University that create enzymes from phage. Purified recombinant phage enzymes can be used as
separate antibacterial agents in their own right.

Phage Therapy also has the potential of preventing or treating infectious diseases of corals. This
could assist with decline of coral around the world.

The high bacterial strain specificity of phage therapy may make it necessary for clinics to make
different cocktails for treatment of the same infection or disease because the bacterial
components of such diseases may differ from region to region or even person to person. In
addition, this means that 'banks' containing many different phages must be kept and regularly
updated with new phages.

Further, bacteria can evolve different receptors either before or during treatment; this can prevent
phages from completely eradicating bacteria for as bacteria evolves, bacteriophages must evolve
as well to keep up with the ever changing bacteria. In the case all bacteria is eliminated, the
specific phage might evolve and attack good bacteria in the specific area of injection.

The need for banks of phages makes regulatory testing for safety harder and more expensive
under current rules in most countries. Such a process would make difficult the large-scale use of
phage therapy. Additionally, patent issues (specifically on living organisms) may complicate
distribution for pharmaceutical companies wishing to have exclusive rights over their
"invention", which would discourage a commercial corporation from investing capital in this.

As has been known for at least thirty years, mycobacteria such as Mycobacterium tuberculosis
have specific bacteriophages. No lytic phage has yet been discovered for Clostridium difficile,
which is responsible for many nosocomial diseases, but some temperate phages (integrated in the
genome, also called lysogenic) are known for this species; this opens encouraging avenues but
with additional risks as discussed below.

Funding for phage therapy research and clinical trials is generally insufficient and difficult to
obtain, since it is a lengthy and complex process to patent bacteriophage products. Scientists
comment that 'the biggest hurdle is regulatory', whereas an official view is that individual phages
would need proof individually because it would be too complicated to do as a combination, with
many variables. Due to the specificity of phages, phage therapy would be most effective with a
cocktail injection, which is generally rejected by the U.S. Food and Drug Administration (FDA).
Researchers and observers predict that for phage therapy to be successful the FDA must change
its regulatory stance on combination drug cocktails. Public awareness and education about phage
therapy are generally limited to scientific or independent research rather than mainstream media.

The negative public perception of viruses may also play a role in the reluctance to embrace
phage therapy.

References

https://www.ncbi.nlm.nih.gov/pubmed/15143702

https://aac.asm.org/content/45/3/649