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An Alternative for Antibiotics: Phage Therapy (PT)
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The discovery of penicillin in the late 1930’s brought along new advances in medicine and extensive
use of antibiotics. Within a few years bacteria became resistant to antibiotics, and thus became ineffectiveBack in the 1930’s? A few years after the discovery? Say what? (Kunin, 1993). In a monthly scientific journalyou don’t say this! Where is the transtion? Something like: This is evident if one looks at…, Antimicrobial
Agents and Chemotherapy (AAC), the number of papers concerning antimicrobial resistance increased from
11% in 1972 to 34% in 1997 (Swartz, 2000).-So we are not talking about the 1930’s? We are talking about
now? Even novel antibiotics like what? Be specific. Where is the evidence. Do not make claims without
evidence. cannot keep pace with the ever-growing numbers of resistant bacteria. This poses a great challenge
to the medical community, and a pressing need exists to find suitable alternatives. You need to improve this
account of antibiotics. Phage therapy (PT) potentially offers such a substitute. Phages, or bacteriophages, are
viruses that infect bacterial cells and kill them, including those that are resistant to antibiotics (Gorski, 2009;
Hanlon, 2007).-This last sentence, should it be here? It hangs in the middle of nowhere. This should be in your
next paragraph. Improve the antibiotic intro/history.
Phages are found in aquatic environments and have evolved with bacteria. There are lysogenic and
lytic phages.-I just read this to my grandma over the phone and all I heard was silence… They are dependent
on bacteria to replicate, and invade their host to assemble new phages with the bacteria’s machinery. I am
stopping here. This is not understandable to the general reader. You need to think about the reader. Lytic?
Lysogenic? I don’t think so. In PT lytic phages are used. The life cycle of these phages begins with its
attachment to their host. These viruses are very specific, and each will only attach to one type of bacteria. The
bacteriophage then inserts its DNA into the host, which carries instructions to make new phage particles.
Using the tools of the bacteria and the instructions from the phage, viral components are made inside the
bacteria. In the final step, the bacterial cell lyses, or explodes, releasing all the phages and killing the host.
Over 100 phages are released each time a cell lyses, each with the ability to begin the cycle again and invade
and kill more bacteria (Hanlon, 2009).
PT is actually not a new finding but it is going through a revival of interest. In fact, they were used
decades before antibiotics to treat bacterial infections. D’Herelle, a scientist from Paris in 1910 co-discovered
bacteriophages and promoted PT. He coined the name “bacteriophage,” meaning that the phages “eat”
bacteria (Sulakvelidze, 2001). D’ Herelle and other scientists made a number of successful PT studies. The
first time D’Herelle used bacteriophages therapeutically was in 1919. He treated a 12-year-old boy with
dysentery and saw recovery within 24 hours. However, a number of negative results were acquired and led to
a decline of PT. The wrong phages were selected to use against their specific host. Sometimes lysogenic
phages were used instead of lytic ones, and often they were also not properly prepared to use for treatment.
The lack of understanding for phages at that time resulted in poorly done experiments with controversial
conclusions. At the same time antibiotics were discovered which seemed simpler and more effective. These
combined effects caused the west to close its door on clinical use and research on PT. However, research
continued in the former Soviet Union and Eastern Europe as antibiotics became popular in the West (Hanlon,
2007).
The research that sustained in Europe were not all highly controlled, and do not reach the modernday standards of investigation but results are still valuable. Numerous publications for the use of PT in
humans are available. A notable extensive study in the Soviet Union tested for the effectiveness of Shigella
phages against bacterial dysentery. A total of 31,000 children in the streets less than seven years old were
used in this study. On one side of the street 17,000 children were given Shigella phages and 13,000 children
on the other side of the street did not receive any. It was observed that the infections were reduced by 2.6
fold in the treated children. Many more clinical studies were conducted, demonstrating the effectiveness of
phages. To name a few, they were used to treat surgical wound, urinary tract, eye, and staphylococcal lung
infections (Sulakvelidze, 2001). In 1952, the Hirszfeld Institute was established in Poland. There,
bacteriophages were produced and studied and a large number of publications come from this institute. Since
then, they have also taken steps to bring PT to patients who have had failed antibiotic treatment
(Sulakvelidze, 2001; Gorski, 2007).
The relatively recent comeback of PT came about in the west when resistant antibiotic pathogens
became an increasing challenge. The clinical studies in Europe helped bring along this revival. In contrast to
research in the past these studies are controlled and meet current standards of investigation (Gorski, 2009).
A study done by Capparelli, et al. (2007) observed the use of PT in mice to kill staphylococcal bacteria that
were resistant to antibiotics. This pathogen causes many dangerous and life threatening symptoms including
inflammation, abscesses (swelling/sores), and pneumonia. The authors concluded from this study that the
phage was able to rescue 97% of the mice, and eliminate the bacteria. Even when the phage was given 10
days after the mice were infected, the phage was successful in killing the bacteria. Additionally, the study
found that there were no side effects from treatment, and the mice were all healthy when the trials ended.
Many more similar studies confirm the effectiveness of this therapy.
There is concern whether PT may find the same future as antibiotics; wouldn’t bacteria develop
resistance to bacteriophages just like they did with antibiotics? Many papers have addressed and given
different solutions to this issue. In comparison to antibiotics, in a shorter period of time bacteria can resist
greater amounts of antibiotics than they can resist phages (Hanlon, 2007). Harcombe and Bull (2005) also
tested whether using several types of phages at once can reduce the chances of resistance. They concluded
that when phages are used against two species of bacteria, the competition between the bacterium reduces
the bacteria’s ability to develop resistance to their specific phage. Moreover, if resistance does develop it
should be possible to isolate a new strain of phage quickly because of their abundance on this planet
(Sulakvelidze, 2001).There are 1032 bacteriophages on earth, which is ten times more than bacteria (Hanlon,
2007).
Another setback to using PT is the reticuloendothelial system (RES) in bacteria. The RES removes
viruses from the organism to a number insufficient to kill the host. In 1996 Merril et al., proposed a way to
select phages that are capable of avoiding removal by the RES. This method which they called the “serial
passage” works similarly to natural selection. Compared to the original, the processed phages were more
successful in treating the infected mice (Merril, et al., 1996).
PT is currently is being considered for regular clinical treatment. There have been steps taken to
evaluate their effect on humans. In 2005 the first safety test in recent English literature for oral phages was
conducted. The scientists concluded from the data that phages can be safely administered with no severe side
effects (Bruttin, et al, 2005). To have a chance of success with PT there are a number of steps to be taken.
More undisputable evidence is needed from basic research and clinical trials. Furthermore, centers
specialized in PT could be established similar to the one in Poland (Gorski, 2009). With the knowledge
accumulated in Europe and the advances made there can be more success in putting PT to use this second
time (Hanlon, 2007).
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References
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Capparelli, R., Parlato, M., Borriello, G., Salvatore, P., Iannelli, D., (2007). Experimental Phage Therapy against
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