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What are
phages and how do they kill bacteria?
Bacteriophages (phages) are viruses that infect bacteria.
Typical phages have hollow heads (where the phage DNA or RNA is
stored) and tunnel tails, the tips of which have the ability to
bind to specific molecules on the surface of their target
bacteria. The phage DNA is then injected through the phage tail
into the host cell, where it directs the production of progeny
phages [See Graphic], often >100 in 30 minutes. These "young"
phages burst from the host cell (killing it) and infect more
bacteria. Click here to see a simulation of the above-described
process (Requires RealPlayer).
Phages are very specific. They can only infect their targeted
bacteria, and they have no effect on any human, other animal,
plant, insect, etc. cells.
How
common are bacteriophages in nature?
Bacteriophages are the most common and ubiquitous organisms
on Earth. Their total number is estimated to be approximately
1032. This value is equal to
100,000,000,000,000,000,000,000,000,000,000 phage particles.
Some additional facts/examples:
- More than 100 million phage species exist
- 1 milliliter of non-polluted water may contain 100,000,000
phages (one milliliter equals one cubic centimeter, or about
two drops from an eyedropper).
- Poultry products, fruits and vegetables, and cheese sold
at retail often contain more than 100,000,000 phages per gram
of food.
- Phages have been found in commercial sera.
- Phages have been found in human vaccines.
- Phages are common in the human mouth, where they are
harbored in dental plaque and saliva.
- Phages are found, in prodigious numbers, in the
gastrointestinal tracts of humans and other animals.
Have
bacteriophages been found in or on foods?
Yes, bacteriophages have been isolated from drinking water
and from a wide range of food products, including ground beef,
pork sausage, chicken, farmed freshwater fish, common carp and
marine fish, oil sardines, raw skim milk, and cheese. In one
published study, bacteriophages were recovered from 100% of
examined fresh chicken and pork sausage samples and from 33% of
delicatessen meat samples. In another study, phages were found
in 48 to 100% of the samples of fresh chicken breasts, fresh
ground beef, fresh pork sausage, canned corned beef, and frozen
mixed vegetables. Several other studies have suggested that 100%
of the ground beef and chicken meat sold at retail contain
various levels of various bacteriophages. Phages also have been
found in animal feed. Humans consume phages daily by drinking
water and by eating unprocessed foods.
Do
organically-grown foods contain phages?
Yes. Organically-grown foods are likely to contain more
phages than do non-organic foods treated with various chemicals,
because many chemicals used to improve the safety of foods, or
to preserve and increase the shelf-life of foods, kill phages as
well as potentially pathogenic bacteria and potentially
beneficial probiotic bacteria.
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Can therapeutic phages be developed against any infection?
Therapeutic phages potentially can be developed against any
bacterial infection. However, because of their "mode of action,"
phages are not effective against viral infections (e.g.,
influenza).
Can any phage be used to develop phage preparations for food
safety applications and for therapeutic use in humans or other
animals?
In general, there are two major types of phages: “virulent”
(also called “lytic”) and “temperate” (sometimes mistakenly
called “lysogenic”). Only virulent/lytic phages are suitable for
therapeutic phage preparations. At the end of their life cycles
inside their specific bacterial host cells, lytic phages release
a burst of progeny phages through the cytoplasmic/outer
membrane, thus lysing the bacteria. On the other hand, some
temperate phages (which, by definition, do not lyse all of their
bacterial host cells) are lysogenic; i.e., they integrate their
DNA into their initial host cell’s DNA and create a “prophage,”
which subsequently may transfer, via the process of
transduction, some of the original host bacterium’s DNA to other
host cells. Such phages are inappropriate candidates for phage
therapy because they do not lyse all of their host cells, and
because they may transfer genes encoding bacterial virulence
factors and resistance to various antibiotics. All phage
preparations developed by Intralytix contain only lytic phages.
How safe are phage preparations developed for therapeutic
applications?
Phages are very safe. They are the most common and ubiquitous
organisms on this planet and humans consume them daily by
drinking water, eating fresh foods, etc. Furthermore, phages
have been used, since 1919, to treat various bacterial
infections of humans and other animals. Large amounts of phages
have been administered, without serious side-effects, to humans:
(i) orally, in tablet or liquid formulations, (ii) rectally,
(iii) locally (skin, eye, ear, nasal mucosa, etc.), in tampons,
rinses and creams, (iv) as aerosols or intrapleural injections,
and (v) intravenously. A few minor side-effects have been
reported in patients undergoing phage therapy, and those that
were seen seemed to be directly associated with the therapeutic
process. For example, mild pain in the liver area (lasting
several hours) was reported in one study conducted in Poland.
The authors suggested that the response was related to extensive
liberation of bacterial endotoxins from the phage-lysed
bacteria. It should be mentioned that this side-effect also may
occur during antibiotic therapy.
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Have phage preparations ever been produced commercially?
Yes. During the 1930s-1940s, Eli Lily and Co. manufactured
several therapeutic phage products for treating various
bacterial infections, including skin infections. Other major
companies involved in therapeutic phage production in the U.S.A.
included E.R. Squibb and Sons and Swan-Myers (now Abbot
Laboratories). In Europe, phage preparations were produced by,
and used for therapy at, the Pasteur Institute (Paris, France),
and the Russian and German Armies routinely used therapeutic
phage preparations during World War II. In fact, phage therapy
has been utilized, from the 1920s to the current day, in Eastern
Europe and the former Soviet Union. At the present time,
therapeutic phage preparations are being manufactured and sold
in some Eastern European countries; e.g., the Republic of
Georgia, Russia, and Poland.
How do
phages compare to antibiotics?
Phages are highly effective in killing their targeted
bacteria (i.e., their action is bactericidal).
Some antibiotics (e.g., chloramphenicol) are bacteriostatic;
i.e., they inhibit the growth of bacteria rather then killing
them, which may help promote emergence of resistance against
those antibiotics.
Phages are very specific, and they affect the targeted
bacterium only; therefore, "dysbiosis" (and chances of
developing secondary infections) is avoided.
Antibiotics are much less specific and they target not only the
pathogenic microorganisms but also a normal microflora. This can
affect the microbial balance in the gut, which, in turn, often
leads to serious secondary infections.
Humans are exposed to phages throughout life, and well
tolerate them. No serious side effects have been described for
therapeutic phages.
Multiple side effects, including yeast infections, intestinal
disorders, and allergies are often associated with antibiotic
therapy.
Because of phages' specificity, their use is not likely to
select for phage resistance in other (i.e., not-targeted)
bacterial species.
Because of their broad spectrum of activity, antibiotics may
select for resistant mutants of many pathogenic bacterial
species, not just for resistant mutants of the targeted
bacteria.
Because of the high specificity of phages, the
disease-causing bacterium has to be identified before the phage
therapy can be successfully employed.
Antibiotic therapy can be initiated without precise
identification of the disease-causing bacterium.
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Can
bacteria develop resistance against phages?
Antibiotic- and phage-resistant mutants of pathogenic
bacteria can arise; however, if that occurs, there are at least
two important factors that favor the development of new,
therapeutically-effective phage preparations. First, since
phages have been co-evolving with bacteria for approximately 3.5
billion years, new lytic phages active against emerging
phage-resistant mutants are constantly arising in the
environment. Therefore, it should be possible to harness the
power of this co-evolutionary process to ensure the continuous
and ready availability/isolation of phages effective against
mutant bacterial pathogens. Second, because the mechanisms by
which antibiotics and phages kill bacteria are very different,
phage therapy will not enhance the emergence of
antibiotic-resistant bacteria, which is a major concern with
antibiotic therapy and with wide-spread use of antibiotics in
agriculture. Thus, phages provide a much needed additional
modality for dealing with bacterial infections, including
infections caused by bacteria that are completely resistant to,
and untreatable with, all currently available antibiotics.
Which phage preparation of Intralytix, Inc. was recently
approved by the FDA?
The United States Food and Drug Administration (FDA) recently
approved a phage preparation (designated “LMP-102™”) developed
by Intralytix, Inc. LMP-102™ is 100% natural, and safe and
effective product for reducing contamination of various
ready-to-eat foods with Listeria monocytogenes; thereby,
increasing their safety for human consumption.
What is LMP-102?
LMP-102™ is an all-natural product that contains six
different bacteriophages isolated from the environment. The
phages in LMP-102™ have not been altered or manipulated in any
way. The preparation specifically targets a foodborne bacterium
called Listeria monocytogenes which kills approximately 500
people each year in the U.S.A alone. Applying LMP-102™ to
various ready-to-eat foods significantly reduces (usually by
99-99.9%) their contamination with this potentially-deadly
bacterium; thereby, increasing their safety for human
consumption.
LMP-102™ is an all-natural product, and media/components of
animal origin are not used during its preparation. In addition,
known, potentially-allergenic substances (wheat, milk, soy,
etc.) are not added to/mixed with the product.
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Does LMP-102 alter the taste or smell of treated foods?
LMP-102™ does not alter the general composition of foods, and
it does not produce any detectable adverse organoleptic changes;
i.e., it does not alter the taste, odor or color of foods
treated with it.
Does LMP-102 extend the shelf-life of treated foods?
LMP-102™ does not affect the shelf-life of treated food. In
other words, it does not extend or shorten the shelf-life of
treated foods.
How is LMP-102 different from the chemicals currently used to
improve food safety?
LMP-102™ specifically kills only Listeria monocytogenes – a
deadly foodborne pathogen – on foods, without affecting the
“good”/beneficial bacteria commonly found on and in various
foods. Using phages to target “bad”/pathogenic bacteria in our
foods without affecting the beneficial bacteria is a possible
breakthrough in the food safety area. We all live in a very
complex environment, in which bacteria play very important
roles. Indeed, although there are many bacteria that can make
people sick or even kill them (e.g., L. monocytogenes which can
cause human illness and kill infected children and pregnant
women), there are even more beneficial bacteria without which
life would not be possible on Earth. Some examples of the latter
bacteria are those in yogurt and other healthy foods, which help
us to digest various foods, synthesize some important nutrients,
enhance immune system function, etc. Traditional approaches for
dealing with potentially pathogenic bacteria include using
antibiotics, irradiation, chemicals, and heat to reduce their
presence. Those approaches effectively kill bacteria; however,
it is important to understand that we can not eliminate all
bacteria and, in fact, it is against our best interests to
attempt to do so. The problem, however, has been the lack of
commercial products that specifically target/kill pathogenic
bacteria without disturbing the normal, beneficial bacteria in
the environment and body. However, Mother Nature has such a
tool, which she has been using for billions of years to maintain
the proper balance of various bacteria in the environment. They
are bacteriophages which, in a well-balanced predator-prey
relationship, have been keeping bacteria in check for millennia.
LMP-102™ and similar pathogenic bacteria-targeting,
bacteriophage-based natural products can dramatically improve
the safety of our foods while maintaining their beneficial
bacterial content.
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