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Phage Technology Intralytix is using its core
bacteriophage technology to develop safe and effective products
based on naturally-occurring bacteriophages, for use in food
production and processing, environmental cleanliness, veterinary
applications, and human therapy.
Bacteriophages: the Most Ubiquitous Organisms on Earth
Bacteriophages (or phages for short) are viruses that infect
bacteria. The name was coined by one of the discoverers of
bacteriophages (Felix d’Herelle), by combining the Greek “phago”
meaning “to eat” or “to develop at the expense of,” and
“bacteria.” Phages are the most ubiquitous organisms on Earth,
and they can be found – often in prodigious numbers – in every
living ecosystem. Phages are highly specific for bacteria, and
they can not infect eukaryotic cells; i.e., those of
humans/animals and plants. Moreover, one phage can only infect a
subgroup of strains within the same bacterial species, without
affecting strains of other bacterial species.
Philosophical and Technical Considerations
Intralytix’s phage technology is based on the philosophy that
naturally-occurring bacteriophages provide one of the safest and
most environmentally-friendly, targeted approaches for dealing
with bacterial infections in a variety of settings. Phages are
“Nature’s way” of controlling bacteria on this planet, and they
have played and continue to play a critical role in maintaining
(via a well-balanced predator-prey relationship) microbial
balance in every ecosystem where bacteria are present. Thus,
Intralytix’s philosophy is to use this natural approach to
control pathogenic bacteria in limited, specific settings where
those bacteria may cause human illness or other problems.
Intralytix’s core phage technology stipulates construction of
natural, safe, and effective phage preparations from a library
of well-characterized bacteriophages isolated from the
environment. After they are in Intralytix’s phage collection,
the phages are not genetically engineered or altered in any way.
However, they are rigorously characterized and carefully
selected to produce phage cocktails optimal for specific
applications. At the present time, Intralytix’s library of lytic
bacteriophages is one of the largest and best characterized in
the world. Also, it is continuously being updated with new
phages, in order to include bacteriophages lytic against
additional bacterial pathogens or bacterial strains of
particular concern in specific geographic locations or in
specific food processing or clinical settings.
Phages vs. Bacteria: Mechanisms of Action
Phages are metabolically inert in their extracellular state
and they reproduce by insinuating themselves into the metabolism
of their host bacteria. After phage DNA is injected into the
host cell, it directs the production of progeny phages. These
phages burst from the host cell, killing it, and then infect
more bacteria. There are innumerable types of phages, each
capable of eradicating a specific bacterial host species. Phages
are abundant in the biosphere and they are Nature’s way of
controlling bacteria in virtually every ecosystem where bacteria
are present. Phages only attack bacteria and have absolutely no
effect on human, animal, insect, plant, etc. cells. Even with
bacteria, a phage does not nonspecifically infect and lyse all
bacterial species; rather, it kills strains or a subgroup of
strains within the targeted bacterial species, which makes
targeted therapy possible. Because of this specificity, phages
may be considered the most gentle, natural, and effective way to
target “problem bacteria” in specific settings, without
affecting other bacteria (which often are beneficial) and
without adversely affecting the environment.
The mechanism by which phages kill their specific host
bacteria is commonly called “lysis.” There are four major steps
in the phage-mediated lytic process: (i) Recognition and
binding: the distal tips of a phage’s tail fibers bind
specifically to receptors in the host bacterium’s cytoplasmic
membrane; (ii) Injection: phage DNA is injected from the phage
into the host cell’s cytoplasm; (iii) Multiplication: phage DNA
replication is initiated, phage-specific proteins are
synthesized, and new phages are assembled. During these steps,
the host cell’s DNA transcription is suppressed and its
metabolic resources are directed towards phage replication,
assembly, etc.; (iv) Lysis: very shortly after infection, the
infected cell dies metabolically (i.e., it stops producing ATP).
This leads to membrane-disruption later in the phage’s lytic
cycle, which enables large numbers of newly-assembled phage
particles to be released from the bacterium, and the host cell’s
death. Although the entire process requires approximately 40
minutes (it varies from phage to phage), most lytic
phage-infected cells are metabolically dead by only 20-40
seconds post-injection of phage DNA.
See the schematic/graphical presentation (below) and an
animated simulation (right margin) of the above-described
process.
Click to Enlarge
Areas of Practical Applications
Properly developed and manufactured phage preparations can be
invaluable in controlling “problem bacteria” in various settings
where the bacteria may cause disease or other problems. Thus,
phage preparations can potentially be useful in any setting
where the eradication of problem bacteria is important. While
such areas of applications are numerous, Intralytix has
identified four major areas for product development and
commercialization of its phage-based technology. They are
applications for
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