What are phages and how do they kill bacteria?
Bacteriophages (phages) are viruses that infect bacteria. They are the most abundant microorganisms on earth. Typical phages have hollow heads, where the phage DNA 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, often more than 100 in 20 - 40 minutes. These "young" phages burst from the host cell, killing it, and infect more bacteria.
Phages are very specific. They can only infect their targeted bacteria, and they have no effect on any human, 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:
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.
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 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:
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.
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 USA 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?
|Efficiency||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
|Specificity||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.
|Side Effects||Humans are exposed to phages throughout life, and well
tolerate them. No serious side effects have been described for
||Multiple side effects, including yeast infections, intestinal disorders, and allergies are often associated with antibiotic therapy.|
|Bacterial Resistance||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
|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.|
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 widespread 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 therefore untreatable with all currently available
Which phage preparations of Intralytix, Inc. did the FDA approve?
The United States Food and Drug Administration (FDA) approved three phage preparations (designated "ListShield™", "EcoShield™" and "SalmoFresh™") developed by Intralytix, Inc.
Phage preparations ListShield™, EcoShield™, and SalmoFresh™ are 100% natural, safe, and effective products for reducing contamination of various foods.
ListShield™ (updated LMP-102) is an all-natural product that contains six
different bacteriophages isolated from the environment. The
phages in ListShield™ 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 USA alone. Applying ListShield™ to
various ready-to-eat foods significantly reduces (usually by
99-100%) their contamination with this potentially deadly
bacterium; thereby, increasing their safety for human
consumption. See product
page or contact Intralytix
for more information.
EcoShield™ (updated ECP-100) is an all-natural product that contains three different bacteriophages isolated from the environment. The phages in EcoShield™ have not been altered or manipulated in any way. The preparation specifically targets a foodborne bacterium called Escherichia coli O157:H7, which causes approximately 62,000 foodborne illnesses each year in the USA alone. Applying EcoShield™ to various ready-to-eat foods significantly reduces (usually by 99-100%) their contamination with this potentially deadly bacterium; thereby, increasing their safety for human consumption. See product page or contact Intralytix for more information.
SalmoFresh™ is an all-natural product that contains six different bacteriophages isolated from the environment. The phages in SalmoFresh™ have not been altered or manipulated in any way. The preparation specifically targets the foodborne pathogen Salmonella enterica , which is responsible for approximately 1.4 million infections each year in the USA alone. Applying SalmoFresh™ to various ready-to-eat foods significantly reduces their contamination with this potentially deadly bacterium; thereby, increasing their safety for human consumption. See product page or contact Intralytix for more information.
Does ListShield™, EcoShield™, or SalmoFresh™ alter the taste or smell of treated foods?
ListShield™, EcoShield™, and SalmoFresh™ do not alter the general composition of foods, and they do not produce any detectable adverse organoleptic changes; i.e., they do not alter the taste, odor or color of foods treated with them.
Does ListShield™, EcoShield™, or SalmoFresh™ extend the shelf-life of treated foods?
ListShield™, EcoShield™, and SalmoFresh™ do not affect the shelf-life of treated food. In
other words, they do not extend or shorten the shelf-life of
How are ListShield™, EcoShield™, and SalmoFresh™ different from the chemicals currently used to improve food safety?
ListShield™ specifically kills only Listeria monocytogenes and EcoShield™ specifically kills only Escherichia coli O157:H7. SalmoFresh™ specifically kills only Salmonella enterica. All three deadly foodborne pathogens are killed without affecting the beneficial "good" bacteria commonly found on and in various foods. Using phages to target pathogenic "bad" bacteria in our foods without affecting the beneficial bacteria is a breakthrough in the food safety area. We all live in a very complex environment, in which bacteria play very important roles. Although there are some bacteria that can make people sick or even kill them (including L. monocytogenes and E. coli O157:H7, which both can cause human illness and can kill infected people, particularly children and pregnant women), most bacteria are actually beneficial and without them life would not be possible on Earth. Some examples of beneficial bacteria are those found 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. While those approaches effectively kill bacteria, it is important to understand that we cannot eliminate all bacteria. In fact, it is against our best interests to attempt to do so and herein lies the problem: a lack of commercial products that specifically target and kill pathogenic bacteria without disturbing the normal, beneficial bacteria in the environment and body. 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. ListShield™, EcoShield™, SalmoFresh™, and similar pathogenic bacteria targeting, bacteriophage-based natural products can dramatically improve the safety of our foods while maintaining their beneficial bacterial content.