SUBMITTED BY: GURPREET KAUR ROLL NO: R292A09 REGD NO: 10800522 M.Sc. (HONS)Microbiology M.Phil(219) Ist Semmester

I am Gurpreet Kaur , the student of M.Sc.(hons) microbio-M.Phil seel highly inducted to the person cooperated with me during my work The person to whom I am highly thankful for his expert guidance is DR: RAVINDER SINGH NAGPAL. I could not express my feelings in words for love, effection , blessing rended by my parents. Above all I highly inducted to God without whose grace this little work could never seen the light of the day.

There fore. phages are considered to be the future of microbiology. Phage therapy is widely used to Vancomycin resistence Enterococcus in experimental mice. Bacteriophages lytic cycle which means that the phage destroys its life cycle without integerating into host genome. Phage therapy is use to treat antibiotic resistant bacteria. Phage therapy is also used to treat Staphylococcal skin disease. Now. . The take up metabolic machinery of bacteria and lysis the cell wall and results in death of bacteria. These are preferred over the antibiotics because they have low probability of developing resistence. they are preferred over antibiotics. Various diseases caused by Pseudomonas aeruginose by administerating KPPIO/X3/d orally. Along with humans it alsohelps in bio-control of bacteria in food and feed.Summary: It is the method of antibacterial treatment that harnesses the bacteria killing properties of otherwise harmless viruses or other parts. Now phages are widely use in the bio-control of food and feed.

Phage can confer key phenotypes on their host. ssDNA. or dsDNA between 5 and 500 kilo base pairs long with either circular or linear arrangement. While infection of bacteria used in the fermentation industry can be very problematic and result in financial losses. Typically. Bacteriophages are much smaller than the bacteria they destroy . The term is commonly used in its shortened form. .usually between 20 and 200 nm in size. The genetic material can be ssRNA (single stranded RNA).What are bacteriophages? lBacteriophages (viruses that infect bacteria) are fascinating organisms that have played and continue to play a key role in bacterial genetics and molecular biology.[2] and up to 70% of marine bacteria may be infected by phages. where up to 9×108 virions per milliliter have been found in microbial mats at the surface. dsRNA.[1] Phages are ubiquitous and can be found in all reservoirs populated by bacterial hosts. for example converting a non-pathogenic strain into a pathogen. The phage-bacterium relationship varies enormously: from the simple predator-prey model to a complex. A bacteriophage (from 'bacteria' and Greek φάγειν phagein "to eat") is any one of a number of viruses that infect bacteria. In fact interest in phage and phage gene products as potential therapeutic agents is increasing rapidly and is likely to have a profound impact on the pharmaceutical industry and biotechnology in general over the coming years. phage. and they play a key role in regulating bacterial populations in all sorts of environments. such as soil or the intestines of animals. Phages are estimated to be the most widely distributed and diverse entities in the biosphere. One of the densest natural sources for phages and other viruses is sea water. almost symbiotic relationship that promotes the survival and evolutionary success of both. in other senarios phage infection of bacteria can be exploited for industrial and/or medical applications. One potential application is the use of phage to combat the growing menace of antibiotic-resistant inf. bacteriophages consist of an outer protein hull enclosing genetic material.


isometric Leviviridae Non-enveloped. filamentous Linear dsDNA Fuselloviridae Circular dsDNA Circular ssDNA Circular ssDNA Inoviridae Microviridae Non-enveloped. pleomorphic Rudiviridae Non-enveloped. rodshaped Non-enveloped. rod-shaped Plasmaviridae Enveloped. isometric Linear dsDNA Circular dsDNA Linear dsDNA Circular dsDNA Corticoviridae Non-enveloped. isometric Lipothrixviridae Enveloped. lemonshaped Non-enveloped. short noncontractile tail Podoviridae Linear dsDNA Tectiviridae Non-enveloped.ORDER FAMILY Nucleic acid Siphoviridae Non-enveloped. long nonLinear dsDNA contractile tail Non-enveloped. isometric Linear ssRNA Segmented dsRNA .

coli by a lytic pathway. When the lambda DNA enters the cell the ends join to form a circular DNA molecule. or it can enter a latent prophage state.000 nucleotide pairs and encodes 50-60 different proteins. which destroys the cell. The entrance and exit of the lambda DNA from the bacterial chromosome are site-specific recombination events. . The bacteriophage can multiply in E. Damage to a cell carrying a lambda prophage induces the prophage to exit from the host chromosome and shift to lytic growth (green arrows).The linear double-stranded DNA bacteriophage lambda genome contains about 50.

or plant). that is. On the other hand. They are reported to be especially successful where bacteria have constructed a biofilm composed of a polysaccharide matrix that antibiotics cannot penetrate. phage therapy gives rise to few if any side effects.S. as opposed to drugs. if any. and does not stress the liver. phage mixtures may be applied to improve the chances of success. phage therapies for a variety of bacterial and poly microbial infections are now becoming available on an experimental basis in food science and agriculture. however. and does not stress the liver. Because phages replicate in vivo. then the term "biocontrol" (as in phage-mediated biocontrol of bacteria) is sometimes employed rather than "phage therapy". Th An important benefit of phage therapy is derived other countries. Thus. and it should not affect the beneficial normal flora of the host. this specificity is also a disadvantage: A phage will only kill a .Phage therapy: Phage therapy is the therapeutic use of lytic bacteriophages to treat pathogenic bacterial infections. particularly in the country of Georgia. animal.S. U. Phage therapy has many potential applications in human medicine as well as dentistry. but also other beneficial bacteria. or clinical samples can be taken and an appropriate phage identified and grown. . small dose is theoretically efficacious. including the e principles of phage therapy have potential applications not only in human medicine. side effects. Phage therapy also has few. They also have a high therapeutic index. this specificity may also be disadvantageous because a specific phage will only kill a bacterium if it is a match to the specific subspecies. so can be chosen to be harmless to not only the host organism (human. Phages are currently being used therapeutically to treat bacterial infections that do not respond to conventional antibiotics. reducing the chances of opportunistic infections. as opposed to drugs. veterinary science. Theoretically. An important theoretical benefit of phage therapy is that bacteriophages can be much more specific than more common drugs. a smaller effective dose can be used. a single. but also in dentistry. phage therapy is harmless to the eucaryotic host undergoing therapy. Since phages are self-replicating in their target bacterial cell. Phage therapy is an alternative to antibiotics being developed for clinical use by research groups in Eastern Europe and the U. from the observation that bacteriophages are much more specific than most antibiotics that are in clinical use.[1] If the target host of a phage therapy treatment is not an animal. and agriculture. veterinary science. such as gut flora. On the other hand. After having been extensively used and developed mainly in former Soviet Union countries for about 90 years.

A Georgian. commercialization of phage therapy was undertaken by the large pharmaceutical company. Eli Lilly. The success rate was as good as. Russian scientists continued to develop already successful phage therapy to treat the wounds of soldiers in field hospitals. Thus.g. Whilst knowledge was being accumulated regarding the biology of phages and how to use phage cocktails correctly. In the USA during the 1940s. this knowledge was not translated and did not proliferate across the world. [citation needed] In the West. extensive research and development soon began in this field. particularly in the country of Georgia. Georgia. Phage therapy is today a widespread form of treatment in neighbouring countries. no therapies are currently authorized for use on humans.[7] Isolated from Western advances in antibiotic production in the 1940s. due to the scientific barriers of the Cold War. phage mixtures are often applied to improve the chances of success.bacterium if it is a match to the specific strain. When antibiotics were discovered in 1941 and marketed widely in the USA and Europe. although phages for killing food poisoning bacteria (Listeria) are now in use.[2][3][4] They tend to be more successful than antibiotics where there is a biofilm covered by a polysaccharide layer. with phages. For 80 years Georgian doctors have been treating local people. George Eliava. Georgia. He travelled to the Pasteur Institute in Paris where he met d'Hérelle. and in 1926 he founded the Eliava Institute in Tbilisi.[8][9] There is an extensive library and research center at the Eliava Institute in Tbilisi. or samples can be taken and an appropriate phage identified and grown. dysentery and gangrene. if not better than any antibiotic. which antibiotics typically cannot penetrate. In neighbouring countries including Russia. phage therapy was immediately recognized by many to be a key way forward for the eradication of bacterial infections. Phages are currently being used therapeutically to treat bacterial infections that do not respond to conventional antibiotics. However. During World War II. including babies and newborns. .[5] HISTORY: Following the discovery of bacteriophages by Frederick Twort and Felix d'Hérelle[6] in 1915 and 1917. early uses of phage therapy were often unreliable. [citation needed] Russian researchers continued to develop and to refine their treatments and to publish their research and results. the Soviet Union used bacteriophages to treat many soldiers infected with various bacterial diseases e. was making similar discoveries. Western scientists mostly lost interest in further use and study of phage therapy for some time. devoted to the development of phage therapy.

.[16] Potential benefits: A potential benefit of phage therapy is freedom from the severe adverse effects of antibiotics. coli.[12] Recent studies have provided additional support for these findings. along with other strategies. [17] Traditional antibiotics usually have more wide-ranging effect. however. there is renewed interest worldwide in the ability of phage therapy to eradicate bacterial infections and chronic polymicrobial biofilm. in human medicine. This might possibly be therapeutically significant. Another benefit of phage therapy is that although bacteria are able to develop resistance to phages the resistance might be easier to overcome. once the exact bacteria are identified and the phages administered. definitive proof for the efficiency of these phage approaches in the field or the hospital is only provided in a few cases. to combat infections such as meningitis. where the blood brain barrier can be crossed — and multiply in the presence of an appropriate bacterial host. Lactococcus and Vibrio pathogens in fish from aquaculture and Erwinia and Xanthomonas in plants of agricultural importance. targeting only one or a few strains of bacteria. Shigella or Vibrio and against wound infections caused by facultative pathogens of the skin like staphylococci and streptococci.[13] Recently. Phages were used against diarrheal diseases caused by E. Increasing evidence shows the ability of phages to travel to a required site — including the brain. in some cases mount an immune response to the phage (2 out of 44 patients in a Polish trial[18]). The oldest use was.[11] Some of the interest in the West can be traced back to 1994. However the patient's immune system can. when Soothill demonstrated (in an animal model) that the use of phages could improve the success of skin grafts by reducing the underlying Pseudomonas aeruginosa infection. in preliminary in vitro experiments for cells in tissue culture. Recently the phage therapy approach has been applied to systemic and even intracellular infections and the addition of nonreplicating phage and isolated phage enzymes like lysins to the antimicrobial arsenal. Bacteriophages are often very specific. the use of phages as delivery mechanisms for traditional antibiotics has been proposed. killing both harmful bacteria and useful bacteria such as those facilitating food digestion. Phages have been explored as means to eliminate pathogens like Campylobacter in raw food[10] and Listeria in fresh food or to reduce food spoilage bacteria. Escherichia and Salmonella in farm animals.[14][15] The use of phages to deliver antitumor agents has also been described. The specificity of bacteriophages might reduce the chance that useful bacteria are killed when fighting an infection. Also it would possibly be fast-acting. However. [11] In agricultural practice phages were used to fight pathogens like Campylobacter.As a result of the development of antibiotic resistance since the 1950s and an advancement of scientific knowledge.

. or used during surgical procedures. The phage showing lysis are then amplified on cultures of the target bacteria. intravenous or intranasal of phages in vivo has been shown to work in laboratory tests. The bacteria usually die. Phages in practice are applied orally. then distributed.Development and production is faster than antibiotics.[citation needed] Some bacteria such as multiply resistant Klebsiella pneumoniae have no non toxic antibiotics available.[2] They can also be extracted from corpses. isolation of therapeutic phages can typically require a few months to complete. otitis etc. Injection is rarely used. phage-impregnated sutures. The phages collect on the top of the mixture and can be drawn off. preventative treatment for burn victims. Enzobiotics are a new development at Rockefeller University that create enzymes from phage. on condition that the required recognition molecules are known. phage treatment works by collecting local samples of water likely to contain high quantities of bacteria and bacteriophages. pneumonia developing with patients suffering from flu. Occasionally. Treatment: Phages are "bacterium specific" and it is therefore necessary in many cases to take a swab from the patient and culture it prior to treatment. The samples are taken and applied to the bacteria that are to be destroyed which have been cultured on growth medium. for example effluent outlets. The phage solutions are then tested to see which ones show growth suppression effects (lysogeny) and/or destruction (lysis) of the target bacteria. and yet killing of the bacteria via intraperitoneal. avoiding any risks .g. These show potential for preventing secondary bacterial infections e. passed through a filter to remove all but the phages. and the mixture is centrifuged.[citation needed] Research groups in the West are engineering a broader spectrum phage and also target MRSA treatments in a variety of forms .including impregnated wound dressings. but clinics generally keep supplies of phage cocktails for the most common bacterial strains in a geographical area. topically on infected wounds or spread onto surfaces. sewage and other sources. Application Collection: In its simplest form.

in August 2006.[2] In pill form temperature stability up to 55 C. gingivitis. These vials are usually best kept refrigerated. for example. Distribution: Phages can usually be freeze dried and turned into pills without materially impacting efficacy. dysentery. ulcers and infected surgical sites. Lubbock. Other forms of administration can include application in liquid form. coli). including P.[22][23] Documentation of the Phase-1 and Phase-2a study is not available at present. conjunctivitis. phages against Listeria are generally recognized as safe (GRAS status) within the worldwide scientific community and opens the way for other phages to also be recognized as having GRAS status. Texas for an approved cocktail of phages against bacteria. [20] it confirms to the public that. The direct human use of phage might possibly be safe. London for Pseudomonas aeruginosa infections (otitis). sinusitis. Phase 1 clinical trials are underway in the South West Regional Wound Care Center. burns. the United States Food and Drug Administration approved spraying meat with phages.of trace chemical contaminants that may be present from the bacteria amplification stage. aeruginosa. periodontitis. as this increases the number of phages surviving passage through the stomachTopical administration often involves application to gauzes that are laid on the area to be treated Obstacles: General .also polymicrobial biofilms on chronic wounds.[ Oral administration works better when an antacid is included. Phage therapy has been attempted for the treatment of a variety of bacterial infections including: laryngitis.[2] . Phase 2a clinical trials have been reported at the Royal National Throat. and shelf lives of 14 months have been shown. suggestively. Nose and Ear Hospital. Staphylococcus aureus and Escherichia coli (better known as E.[21]. etc. urinary tract infections and intestinal infections.and recognizing that the immune system naturally fights against viruses introduced into the bloodstream or lymphatic system. skin infections. Although this initially raised concerns since without mandatory labeling consumers won't be aware that meat and poultry products have been treated with the spray.[citation needed] Reviews of phage therapy indicate that students should aware of this.[citation needed] In 2007. boils.

endotoxins are released by the bacteria as they are destroyed within the patient (Herxheimer reaction). a phage-therapy start-up in Bangalore. In addition. for example Clostridium and Mycobacterium. which makes regulatory testing for safety harder and more expensive. phage therapy would be most effective with a cocktail injection. Scientists comment that 'the biggest hurdle is regulatory'. since it is a lengthy and complex process to patent bacteriophage products. Without this gene the host bacterium still . due to the specificity of individual phages. This can cause symptoms of fever. whereas an official view is that individual phages would need proof individually because it would be too complicated to do as a combination. have no known therapeutic phages available as yet. a former president of AstraZeneca India who 2 years ago launched GangaGen Inc. Such a process would make it difficult for large scale production of phage therapy. The negative public perception of viruses may also play a role in the reluctance to embrace phage therapy Safety: Phage therapy is generally considered safe. Public awareness and education about phage therapy are generally limited to scientific or independent research rather than mainstream media. Funding for phage therapy research and clinical trials is generally insufficient and difficult to obtain. or in extreme cases toxic shock (a problem also seen with antibiotics) is possible Janakiraman Ramachandran. and viruses do not necessarily reach the same places that antibiotics can reach. a mixture of phages is often applied.. Additionally. To work. Due to the specificity of phages. Researchers and observers predict that for phage therapy to be successful the FDA must change its regulatory stance on combination drug cocktails.The host 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. This means that 'banks' containing many different phages are needed to be kept and regularly updated with new phages. patent issues (specifically on living organisms) may complicate distribution for pharmaceutical companies wishing to have exclusive rights over their "invention". for a high chance of success. which are generally rejected by the FDA. with many variables. argues that this complication can be avoided in those types of infection where this reaction is likely to occur by using genetically engineered bacteriophages. which have had their gene responsible for producing endolysin removed. Some bacteria. As with antibiotic therapy and other methods of countering bacterial infections. making it unlikely that a for-profit corporation will invest capital in the widespread application of this technology. the virus has to reach the site of the bacteria.

Phage display: 1.[1] This connection between genotype and phenotype enables large libraries of proteins to be screened and amplified in a process called in vitro selection. so one administered phage means one dead bacterial cell. Phage display is a method for the study of protein-protein. Lysogenic bacteriophages are not generally used therapeutically. The lytic bacteriophages available for phage therapy are best kept refrigerated but discarded if the pale yellow clear liquid goes cloudy. coli cells until they are infected with helper phage. . [2][3] though T4. phage display is used for the high-throughput screening of protein interactions. protein-peptide.] Eventually these dead cells are consumed by the normal house cleaning duties of the phagocytes. T7. The most common bacteriophages used in phage display are M13 and fd filamentous phage. the DNA encoding the protein or peptide of interest is ligated into the pIII or pVIII gene. In the case of M13 filamentous phage display. can make the bacteria pathogenic (see Cholera). coli bacterial cells such as TG1 or XL1Blue E. polysaccharides and lipidsCare has to be taken in manufacture that the phage medium is free of bacterial fragments and endotoxins from the production process. theoretically. The incorporation of many different DNA fragments into the pIII or pVIII genes generates a library from which members of interest can be isolated. which utilise enzymes to break the whole bacterium and its contents down into its harmless sub-units of proteins. which enables packaging of the phage DNA and assembly of the mature virions with the relevant protein fragment as part of their outer coat on either the minor (pIII) or major (pVIII) coat protein. which is analogous to natural selection. and this can help spread antibiotic resistance or even. On the other hand this modification stops the exponential growth of phages. The phage gene and insert DNA hybrid is then transformed into E.dies but remains intact because the lysis is disabled. and protein-DNA interactions that utilizes bacteriophage to connect proteins with the genetic information that encodes them. This group can act as a way for bacteria to exchange DNA. Principle: Like the two-hybrid system. Multiple cloning sites are sometimes used to ensure that the fragments are inserted in all three possible frames so that the cDNA fragment is translated in the proper frame. coli. and λ phage have also been used. The phage particles will not be released from the E.

and following further bacterial-based amplification. This phage-display library is added to the dish and after allowing the phage time to bind.e. It is used . Phage display is also a widely used method for in vitro protein evolution (also called protein engineering). phage display is a useful tool in drug discovery. non-binding phage) than were present in the initial mixture. Phage-displaying proteins that interact with the target molecules remain attached to the dish. 3. in reference to the enrichment of a sample of gold by removing undesirable materials. tissue or organism) so that new functions or mechanisms of function of that protein may be inferred [5]. 5. while all others are washed away.. 4. shows that use of the helper phage can be eliminated by using a novel 'bacterial packaging cell line' technology General protocol: 1. The technique is also used to determine tumour antigens (for use in diagnosis and therapeutic targeting)[6] and in searching for protein-DNA interactions[7] using specially-constructed DNA libraries with randomised segments. The new phage constitutes an enriched mixture.e. can be sequenced to identify the relevant. 2. Recent work published by Chasteen et al. Those that remain can be eluted. microtiter plate. The DNA within the interacting phage contains the sequences of interacting proteins. so that they are displayed on the surface of the viral particle. used to produce more phage (by bacterial infection with helper phage) and so produce a phage mixture that is enriched with relevant (i. The repeated cycling of these steps is referred to as 'panning'. from which the phagemids can be collected and the relevant DNA sequence excised and sequenced to identify the relevant. As such. Attached phage may be eluted and used to create more phage by infection of suitable bacterial hosts. containing considerably less irrelevant (i. binding) phage. a phage that displays a protein that binds to one of those targets on its surface will remain while others are removed by washing.By immobilising a relevant DNA or protein target(s) to the surface of a well. The protein displayed corresponds to the genetic sequence within the phage. interacting proteins or protein fragments. Phage eluted in the final step can be used to infect a suitable bacterial host. Target proteins or DNA sequences are immobilised to the wells of a Many genetic sequences are expressed in a bacteriophage library in the form of fusions with the bacteriophage coat protein. 6. Applications: The applications of this technology include determination of interaction partners of a protein (which would be used as the immobilised phage "bait" with a DNA library consisting of all coding sequences of a cell. the dish is washed. interacting proteins or protein fragments.

is any virus that infects bacteria. and K" Bacteria-Eating Virus Approved as Food Additive: Not all viruses harm people. Bacteriophage means "bacteria eater. monocytogenes). The Food and Drug Administration has approved a mixture of viruses as a food additive to protect people. monocytogenes can cause an infectious disease. Pregnant women are about 20 times more likely than other healthy adults to get listeriosis. The additive can be used in processing plants for spraying onto ready-to-eat meat and poultry products to protect consumers from the potentially life-threatening bacterium Listeria monocytogenes (L. As a long-term solution. and mRNA display. Short-term borderline solutions under the responsibility of a Medical Ethical Committee and/or under the umbrella of the Declaration of Helsinki are emerging. ribosome display. The viruses used in the additive are known as bacteriophages.for finding new ligands (enzyme inhibitors. bacterial display. older people. we suggest the creation of a specific section for phage therapy under the Advanced Therapy Medicinal Product Regulation to papain yields potent peptide inhibitors of cathepsins L. Very few new antimicrobials are in the pharmaceutical industry pipeline. H. B. Consuming food contaminated with the bacterium L. also called a phage (pronounced fayj). The treatment of infectious diseases with antibiotics is becoming increasingly challenging. Major obstacles for the clinical application of bacteriophages are a false perception of viruses as ‘enemies of life’ and the lack of a specific frame for phage therapy in the current Medicinal Product Regulation. newborns. but can be severe and even deadly in pregnant women. One of the potential alternatives for antibiotics is phage therapy. and people with weakened immune systems. listeriosis. which is rarely serious in healthy adults and children. receptor agonists and antagonists) to target proteinsCompeting methods for in vitro protein evolution are yeast display." A bacteriophage. according to the Centers for Disease Control and . however.

Andrew Zajac." says Zajac. loss of balance. "They'll only thrive if Listeria are present. sausages. which seek out other bacteria to invade and repeat the cycle. stillbirth. forcing it to produce hundreds of new phages and causing the bacterial cell walls to break open. and they are part of the microbial population in the human gut and oral cavity. which means that the phage destroys its host during its life cycle without integrating into the host genome. monocytogenes. "We're routinely exposed to bacteriophages. says Zajac.Prevention (CDC). but many ready-to-eat foods. such as hot dogs." How Bacteriophages Work? Bacteriophages are found in the environment. the bacteria can continue to multiply. They need a host to multiply and will gradually become inactive when they lose the host." Thousands of varieties of phages exist. and other deli-style meats and poultry. about 500 die." The type of phage that was approved is lytic. "The process continues until all host bacteria have been destroyed. or convulsions can occur. The phage takes over the metabolic machinery of the bacterium." . "L. "They don't infect plant or mammalian cells. Cooking can kill L. "If a food product contaminated with L. monocytogenescan continue to thrive even in refrigerated conditions. and sometimes an upset stomach. This type of phage works by attaching itself to a bacterium and injecting its genetic material into the cell. and each one infects only one type or a few types of bacteria. premature delivery." says Capt. monocytogenesis bought by a consumer and brought home and refrigerated. The CDC estimates that about 2." Bacteriophages infect only bacteria. If the infection spreads to the nervous system. confusion. so the L. "They are found in soil and water. Listeriosis can cause miscarriage. stiff neck. The particular phages approved as a food additive are very specific to Listeria. "Then the bacteriophages cease replicating. Unlike fresh meat and poultry. luncheon meats. says Zajac. People with listeriosis have fever and muscle aches. Of these. may become contaminated within the processing plant after cooking and before packaging. or death of a newborn baby." says Zajac. monocytogenes survive and are ingested. and diarrhea. nausea. cold cuts. the ready-to-eat products can be consumed without reheating.500 people become seriously ill with listeriosis each year in the United States. This process kills the bacterium and releases many new phages. a food safety expert and acting director of the Division of Petition Review within the FDA's Center for Food Safety and Applied Nutrition (CFSAN). headache.

In response to a petition submitted by industry. any company can use the additive. The preparation combines six different phages that have been shown to be effective against 170 different strains of L. Department of Agriculture (USDA) are involved in the approval." says Robert C. Post." The FDA's CFSAN determined that the phage preparation does not pose any safety concerns based. both the FDA and the U. Once a food additive is approved. monocytogenes. monocytogenes develop resistance to several phages. The USDA's Food Safety and Inspection Service (FSIS) evaluated the bacteriophage preparation's suitability. director of the FSIS' Labeling and Consumer Protection Staff. The FDA must approve any additive before it can be used in food. Ph. in part. the USDA evaluates the ingredient's suitability. a manufacturer must petition the FDA for its approval. the FDA published a regulation in August 2006 permitting the use of a Listeria-specific bacteriophage preparation on ready-to-eat meat and poultry products.S. on published reports submitted by the petitioner on the results of the use of phages in animal and human studies. The FDA evaluates the safety of the ingredient for its intended use. the remaining ones can still destroy the bacteria. The FDA's food additive regulations define safety as "a reasonable certainty that the substance is not harmful under the intended conditions of use. which will ensure that the additive used in food is the same substance that was evaluated and approved by the FDA.D. Multiple phages are used so that if the L. At the same time. says Zajac.. If an additive is approved. The regulation also provides the additive's identity and specifications on purity. When an additive is to be used on meat or poultry products. The petition must provide convincing evidence that the proposed additive performs as it is intended and will not cause harmful effects when consumed. as with this one. In addition.Approval Process Additives: for Food To market a new food additive. "Suitability establishes that the use of a substance is effective in performing the intended purpose of use and at the lowest level necessary for particular types of products. suitability is an assurance that the use of the . as long as it meets the conditions in the regulation. the FDA issues a regulation that includes information on the types of foods in which the additive can be used and maximum amounts to be used.

The number of viable P. The FSIS evaluated data submitted by the petitioner to ensure suitability for a number of ready-to-eat products.additive will not result in a product that is unfit for human consumption (adulterated) or one that misleads consumers. but only under limited experimental conditions. our findings suggest that oral administration of phage may be effective against gut-derived sepsis caused by P. 66. such as sausages. hot dogs. both administered by the USDA. soups. such as spraying on crops. The levels of inflammatory cytokines (tumor necrosis factor alpha TNF-alpha. Mice treated with phage also had lower numbers of viable P. Phages are currently approved in the United States for pesticide applications. for example. Vienna sausage.01). says Post. interleukin-1beta [IL-1beta]. In conclusion. and IL-6) in blood and liver were significantly lower in phage-treated mice than in phage-untreated mice. Labeling: Under the Federal Meat Inspection Act and the Poultry Products Inspection Act.7% for the phage-treated group versus 0% for the saline-treated control group. aeruginosa cells in fecal matter in the gastrointestinal tract was significantly lower in phage-treated mice than in the saline-treated control mice. P<0." says Post. Oral administration of a newly isolated lytic phage strain (KPP10) significantly protected mice against mortality (survival rates. aeruginosa and found that phage treatment significantly improved the survival of mice. liver. and cooked ham and turkey. turkey. aeruginosa. and spleen. aeruginosa cells in their blood. Consumers would be misled if. "they always have the ability to ask for the label of the product being prepared or sliced to see what it contains. Scientists continue to be interested in other uses for phages. Consumers will see "bacteriophage preparation" on the label of meat or poultry products that have been treated with the food additive. the use of the phage preparation must be declared on labeling as an ingredient. bologna. We also studied the efficacy of phage treatment for intraperitoneal infection caused by P. stews." A Phage First: This approval marks the first time that the FDA has regulated the use of a phage preparation as a food additive. the additive makes a product "appear to be a better value than it actually is or it masks spoilage. The efficacy of bacteriophage (phage) therapy by using a murine model of gut-derived sepsis caused by Pseudomonas aeruginosa that closely resembles the clinical pathophysiology of septicemia in humans. such as to prevent food products from contamination with other types of harmful bacteria and to act as possible treatments for bacterial infections in people. .If consumers have any concerns about what they're getting at the deli counter.

clinicians and biotechnologists currently researching or putting bacteriophages to practical use are able to pool their knowledge and expertise and thereby accelerate progress towards further development in this exciting field of biotechnology. . they have been extensively used to prevent and treat bacterial infections.Bacteriophages are viruses that only infect bacteria. It is hoped that the wide range of scientists. led to an eclipse in the use of phage in medicine. However. They have played an important role in the development of molecular biology and have been used as anti-bacterial agents. This diversity and ease of manipulation and production means they have potential research. coupled with doubts about the efficacy of phage therapy. Exploiting phages for production of vaccines : Bacteriophages have a number of potential applications in the biotechnology industry. This brief review aims to describe the history of bacteriophage and early clinical studies on their use in bacterial disease prophylaxis and therapy. One of the possible replacements for antibiotics is the use of bacteriophages as antimicrobial agents. has resulted in a renewed interest in alternatives to conventional drugs. as alternatives to antibiotics. Since their independent discovery by Twort and d'Herelle. therapeutic and manufacturing uses in both the biotechnology and medical fields. and discuss the advantages and disadvantages of bacteriophage in this regard. especially strains that are multiply resistant. mainly in Eastern Europe and the former Soviet Union. the discovery and widespread use of antibiotics. The emergence of antibiotic resistant bacteria. In western countries this method has been sporadically employed on humans and domesticated vehicles for protein and DNA vaccines. for gene therapy. and as protein/antibody library screening tools.

Apparent safety. Low probability of developing resistence. Completely new peptidoglycan . .Conclusion: • • • • • • • whole phage therapy or part therapy are promising . Very rapid and potent antibacterial activity in vitro and vivo against Gram positive bacteria. mode of action and enzymatic cleavage of A narrow antibacterial specterum.

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