Love Me Love My Phages -Bacteriophages - The New Antibiotics-Part3

 


One in six will live to be 100:


Official figures predict 10m alive today will

 get royal telegram



By Becky Barrow



Last updated at 8:11 AM on 31st December 2010



One in six people in Britain will live to celebrate their 100th birthday, official figures reveal today.

More than 10million of the current population will receive a royal telegram, with many even surviving until 110.



Improved diets, living conditions and medical technology are driving the dramatic demographic transformation.



People of all ages, whose grandparents may have died in their 60s and so barely knew them, are increasingly likely to live until they reach the milestone.
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The figures – from the Department for Work and Pensions – show that 17 per cent of the population will see their 100th birthday, equal to about 10.6million people.
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Of these, around three million are currently under 16. Around 5.5million are between 16 and 50, and around 1.3million are between 51 and 65.
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There are also about 875,000 who have already celebrated their 65th birthday and can expect to live for at least another 35 years. 
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Last year there were just 11,600 people aged 100 or above, a figure which itself was more than four times that recorded 30 years before.
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Even over the past two years the ranks of centenarians have swelled by nearly 25 per cent.

w statistics reveal that more than 10million of the current population will reach the age of 100 and receive a royal telegram
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And when the current generation of centenarians was being born in the years before the First World War, only 100 people were thought to have reached their century.

The astonishing increase in longevity raises worrying questions about how the State will cope in supporting so many old people. And there will be concerns about how many will be able to afford a decent standard of living for such a long retirement.
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It raises the prospect of millions surviving until their 100th birthday with a very poor quality of life due to poor health.
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Last month the Office for Budget Responsibility warned spending on old people is ‘unsustainable’.

At present, about 22.5 per cent of Britain’s economic output goes on ‘aged-related expenditure’ such as pensions and the NHS.
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This is expected to reach a crippling 27.1 per cent by 2050.
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The Government has already revealed plans to raise the pension age for men and women to 66 and scrap rules which allow bosses to force workers out when they reach 65.
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But the age is likely to keep on going up in an attempt to cut the massive cost of paying the state pension, currently £97.65 per week.
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Fewer than a third of private sector workers have a company pension. Millions

of older people have no pension, no savings, no other investments and no plan about how they are going to pay for their retirement other than to carry on working.
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To make matters worse, many have not paid off the mortgage on their property, or are renting at a time when tenants are paying record sums.
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Steve Webb, pensions minister, said: ‘These staggering figures really bring home how important it is to plan ahead for our later lives.
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‘Many millions of us will be spending around a third of our lives or more in retirement.’

Over the last 50 years life expectancy has been transformed by the availability of better medicine on the NHS.
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Experts say modern treatments such as statins, which lower blood cholesterol, and blood pressure drugs are helping to prevent fatal conditions and increase lifespan.
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Better education and greater awareness of diet have helped many stay healthier. And the decline of jobs requiring heavy and risky manual work has also played a part.
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By 2066, there will be around 7,700 ‘super-centenarians’ – those who have reached at least 110.

A baby girl born in 1981 could typically expect to live until she was 76, and one born today can expect to live until she is 82. But one born in 2020 will have an average life expectancy of nearly 85, and by 2058 it will be nearly 90.
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The DWP said its ‘Centenarian Clerk’, who works with Buckingham Palace to ensure that everyone who reaches 100 receives a birthday card from the Queen, will be ‘very busy’.
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Dr Ros Altmann, director general of The Saga Group, the old age specialists, said: ‘Many people face decades of struggling to survive with inadequate incomes. 
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‘Savings rates, investment returns and annuity rates have fallen sharply, meaning lower pensions all round.’ 
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A report this month showed that although life expectancy is rising, people are not necessarily healthier during the ‘extra time’ they have gained.
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Data from the UK and the U.S. showed at least one extra year is spent immobile or in poor health, compared with ten to 30 years ago.
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Love Me Love My Phages - - Bacteriophages - The New Antibiotics - Part 3

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 Cholesterol-lowering statins boost bacteria-killing cells

 Posted On: November 17, 2010 - 5:40pm


Science Codex

Widely prescribed for their cholesterol-lowering properties, recent clinical research indicates that statins can produce a second, significant health benefit: lowering the risk of severe bacterial infections such as pneumonia and sepsis. A new explanation for these findings has been discovered by researchers at the University of California, San Diego School of Medicine and Skaggs School of Pharmacy & Pharmaceutical Sciences, who describe for the first time how statins activate the bacterial killing properties of white blood cells.
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The research is published in the November 18, 2010 issue of Cell Host & Microbe.

Led by Victor Nizet, MD, professor of pediatrics and pharmacy, and Christopher Glass, MD, PhD, professor of medicine and cellular & molecular medicine, the UC San Diego team found that phagocytes (white blood cells that kill and ingest harmful bacteria, foreign particles and dead or dying cells) became more effective after being exposed to statins. 

Surprisingly, the statin-induced improvement in bacterial killing did not correspond to increased uptake of bacteria by these specialized white blood cells. Rather, the researchers found that statins stimulated the phagocytes to release "extracellular traps" – specialized webs of DNA-based filaments embedded with anti-microbial peptides and enzymes capable of ensnaring and killing bacteria before they spread in the body. 

The findings have broad ramifications, said Glass, given the popularity of statins for controlling high cholesterol levels. Statins are the world's most-prescribed class of medication. An estimated 30 million Americans alone take the drug under commercial names like Lipitor, Zocor and Crestor. "Clinical research indicates that perhaps 100 million Americans have elevated cholesterol levels that could benefit from statin therapy," said Glass. "Thus any statin-associated changes to immune system function are certain to impact millions of people." 

Prior research had described various anti-inflammatory properties of statins, suggesting that these effects could contribute to a reduction in disease severity during severe infections. Nizet and Glass explored a different hypothesis: That statins might actually aid the body in clearing itself of infectious microbes. The researchers focused on Staphyloccocus aureus, more commonly called "staph," a frequently antibiotic-resistant human pathogen responsible for everything from minor skin infections to life-threatening meningitis and sepsis. Mice treated with statins were more resistant to staph infections, and phagocytes isolated from these mice were more effective at killing staph bacteria. Simple exposure of freshly isolated human white blood cells to statins in a test tube markedly increased their ability to kill staph and other important disease causing bacteria. In each case, the increased killing correlated with greater release of the DNA-based extracellular traps by the phagocytes.

The UCSD findings demonstrate that statins have important pharmacological effects beyond inhibiting cholesterol production. "We found these drugs fundamentally alter how white blood cells behave upon encountering bacteria," Nizet said. "In our studies with staph bacteria, the net effect of statin treatment was to improve bacterial killing and extracellular trap formation. These same changes might not be so consequential for defense against less virulent bacteria that are easily susceptible to uptake and killing within phagocytes."

The research also sheds important new light on the clinical phenomenon of reduced infection severity in patients receiving statins, the scientists said. It indicates that levels of cholesterol or related lipid molecules can be sensed by white blood cells and used as signals to control their inflammatory and antibacterial activities. Nizet and Glass recommend that future research explore whether the potential of cholesterol-lowering agents combined with antibiotics can be harnessed to optimize the treatment of certain difficult infectious disease conditions.


Source: University of California - San Diego
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Love Me Love My Phages - - Bacteriophages - The New Antibiotics - Part 3

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Cholesterol Lowering Statins Kill Bacteria

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Washington, Nov 18 : A recent clinical research suggests that statins, widely prescribed for their cholesterol-lowering properties, can reduce the risk of severe bacterial infections such as pneumonia and sepsis.
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Researchers at the University of California, San Diego School of Medicine and Skaggs School of Pharmacy and Pharmaceutical Sciences, found that phagocytes (white blood cells that kill and ingest harmful bacteria, foreign particles and dead or dying cells) became more effective after being exposed to statins.
⇡
Victor Nizet, professor of pediatrics and pharmacy, and Christopher Glass, professor of medicine and cellular and molecular medicine, the UC San Diego team, led the study.
⇡
The researchers also found that statins stimulated the phagocytes to release "extracellular traps" – specialized webs of DNA-based filaments embedded with anti-microbial peptides and enzymes capable of ensnaring and killing bacteria before they spread in the body. 
⇡
Glass said that the findings have broad ramifications given the popularity of statins for controlling high cholesterol levels. 
⇡
"Clinical research indicates that perhaps 100 million Americans have elevated cholesterol levels that could benefit from statin therapy. Thus any statin-associated changes to immune system function are certain to impact millions of people," said Glass.
⇡
Prior research had described various anti-inflammatory properties of statins, suggesting that these effects could contribute to a reduction in disease severity during severe infections.
The UCSD findings demonstrate that statins have important pharmacological effects beyond inhibiting cholesterol production.
⇡
"We found these drugs fundamentally alter how white blood cells behave upon encountering bacteria. In our studies with staph bacteria, the net effect of statin treatment was to improve bacterial killing and extracellular trap formation. These same changes might not be so consequential for defense against less virulent bacteria that are easily susceptible to uptake and killing within phagocytes," said Nizet.
⇡
The research also sheds important new light on the clinical phenomenon of reduced infection severity in patients receiving statins, the scientists said. It indicates that levels of cholesterol or related lipid molecules can be sensed by white blood cells and used as signals to control their inflammatory and antibacterial activities.
⇡
The research is published in the issue of Cell Host and Microbe. (ANI)

Love Me Love My Phages - - Bacteriophages - The New Antibiotics - Part 3

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Statins Reduce Risk of Sepsis for People on Dialysis

Cholesterol Drugs Reduce Risk of Sepsis
By Mary Anne Dunkin

If you have an inflammatory form of arthritis, such as lupus or RA, reducing your risk of heart disease is crucial. Statins do just that, by lowering cholesterol levels. But they also provide another benefit to people with lupus-related kidney inflammation – called lupus nephritis – by cutting in half the risk of sepsis, a potentially deadly blood infection that can occur in people on dialysis.

In a recent study, dialysis patients taking statins had a 41-in-1,000 chance of being hospitalized for sepsis, while the risk for those not taking statins was 110 out of 1,000. Statins include the medications atorvastatin (Lipitor), fluvastatin (Lescol), lovastatin (Advicor, Mevacor), rosuvastatin (Crestor) and simvastatin (Zocor).

Sepsis is not only a problem for people on dialysis; it is the leading cause of death in hospital intensive care units. Earlier research showed statins reduced sepsis risk in hospitalized people with cardiovascular disease.

Doctors aren't sure how statins work to reduce the risk of sepsis, but suspect they have bacteria-fighting properties unrelated to their effect on cholesterol. However, experts say it's too soon to prescribe statins for sepsis prevention alone.

Source: Lancet, Vol. 367, No. 9508
ARTHRITIS TODAY

Love Me Love My Phages - - Bacteriophages - The New Antibiotics - Part 3

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http://www.celebrities-with-diseases.com/health-news/stanins-help-slow-down-development-of-multiple-sclerosis-4799.html

Statins help slow down development of
multiple sclerosis
 Published: April 17, 2010

A recent study has revealed that statins may help slow down the progression of multiple sclerosis. According to www.phsyorg.com, drugs taken for lowering cholesterol, Statins could be more effective aid for slowing the development of the multiple sclerosis as compared to placebo.

The study was conducted by the researchers at the University of California. Multiple sclerosis (MS) is a condition which takes place when the immune cells in the body attack the nervous system which results in development of lesions in the spinal cord and brain leading to neurological disability.

As per www.food.sify.com, the team of researchers carried out the study on about 81 patients who were diagnosed with multiple sclerosis. These patients were given certain statins for a period of 12 months, which included about five MRI scans at regular intervals. At the end of the study it was found that the percentage of people who did not develop lesions following a treatment of statins was 55.3 percent, while percentage of people who were kept on placebo was 27.6 percent.

"The exciting finding in this study is that reducing new brain MRI lesions should be meaningful for patients since new lesions are reliable correlates of future clinical attacks in MS," remarked Pelletier, one of the researchers.

Celebrities who suffer from multiple sclerosis include comedian Richard Pryor.

More From Celebrities with Diseases

* Richard Pryor dies after long battle with multiple sclerosis
* Regular intake of apple juice helps improve symptoms of Alzheimer’s Disease
* John Candy died of a heart attack aged 43


Love Me Love My Phages - - Bacteriophages - The New Antibiotics - Part 3

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 http://www.medicalnewstoday.com/articles/203418.php

New Way To Fight Superbugs Using
Natural Enzymes In Tears And Other Body
Fluids
 Main Category: MRSA / Drug Resistance
Also Included In: Infectious Diseases / Bacteria / Viruses; Biology / Biochemistry
Article Date: 04 Oct 2010 - 10:00 PDT

In the scramble to find alternative ways to stem the rise of superbugs, scientists from many fields are looking everywhere for solutions, including revisiting one that was proposed over 80 years ago: identifying natural "lytic" enzymes in body fluids like tears and saliva and other sources, that are capable of attacking bacteria, especially antibiotic-resistant ones like MRSA.

Now a new US study, by a team from the Georgia Institute of Technology in Atlanta and the University of Maryland in Rockville, published on 4 October in the Institute of Physics journal Physical Biology, describes the results of a pioneering method that can identify which lytic enzymes are the most effective at killing unfriendly bacteria, including superbugs.

Lytic enzymes were first spotted by Alexander Fleming in 1923, five years before he discovered penicillin; he noticed that enzymes present in mucus samples was capable of killing bacteria. But then penicillin came along, laying the ground for what we now know as antibiotics, and lytic enzymes were quietly forgotten.

However, antibiotic-resistant superbugs now demand that we consider a different approach to the "one size fits all" therapy of current antibiotics, which is considered partly responsible for their rise in the first place.

An advantage of lytic enzymes is that each type targets a limited range of bacteria, so in theory it should be possible to find ones that kill undesirable bacteria while leaving the "friendly" ones alone.

Now study authors Joshua Weitz and Gabriel Mitchell, quantitative biologists at the Georgia Institute of Technology, and Daniel Nelson, a biochemist from the University of Maryland, have shown it is possible on a microscopic scale, to work out how powerful lytic enzymes are at destroying bacteria by finding the rate at which they pierce the bacterial cell walls (the process of "lysis"), thereby causing the organisms to explode to death under the force of their own internal pressure.

In their paper they explained how they observed light passing through a solution of bacteria in a similar way to astrophysicists observing light from far-away galaxies: by measuring the amount and properties of the light they could "infer processes at a far different scale".

Previous attempts to characterize lytic enzymes have used techniques based on synthetic substrates: this has proved difficult because lytic enzymes "bind to the complex superstructure of intact cell walls", wrote the researchers.

The new method developed by Weitz and colleagues, which they described as "based on turbidity assays", allows them to predict the cell level processes of bacterial death by measuring the rate at which the lytic enzymes clear a "cloudy" (turbid) solution of living bacteria, without having to use a synthetic substrate.
 
Love Me Love My Phages - - Bacteriophages - The New Antibiotics - Part 3
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 Phages vs Fireblight Disease

Development of a bacteriophage-based biopesticide for fire blight


http://hdl.handle.net/10464/1448    

abstract    

Fire blight is an economically important disease of apples and pears that is caused by the bacterium Erwinia amylovora. Control of the disease depends on limiting primaly blosson1 infection in the spring, and rapidly removing infected tissue. The possibility of using phages to control E.amylovora populations has been suggested, but previous studies have. failed to show high treatment efficacies. This work describes the development of a phage-based biopesticide that controls E. amylovora populations under field conditions, and significantly reduces the incidence of fire blight.

This work reports the first use of Pantoea agglomerans, a non-pathogenic relative of E. amylovora, as a carrier for E. amylovora.phages. Its role is to support a replicating population of these phages on blossom surfaces during the period when the flowers are most susceptible to infection. Seven phages and one carrier isolate were selected for field trials from existing collections of 56 E. amylovora phages and 249 epiphytic orchard bacteria. Selection of the . /' phages and carrier was based on characteristics relevant to the production and field perfonnance of a biopesticide: host range, genetic diversity, growth under the conditions of large-scale production, and the ability to prevent E. amylovora from infecting pear blossoms. 
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In planta assays showed that both the phages and the carrier make significant contributions to reducirig the development of fire blight symptoms in pear blossoms. Field-scale phage production and purification methods were developed based on the growth characteristics of the phages and bacteria in liquid culture, and on the survival of phages in various liquid media. Six of twelve phage-carrier biopesticide treatments caused statistically signiflcant reductions in disease incidence during orchard trials. Multiplex real-time PCR was used to simultaneously monitor the phage, carrier, and pathogen populations over the course of selected treatments.
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In all cases. the observed population dynamics of the biocontrol agents and the pathogen were consistent with the success or failure of each treatment to control disease incidence. In treatments exhibiting a significantly reduced incidel1ce of fire blight, the average blossom population of E.amylovora had been reduced to pre-experiment epiphytic levels. In successful treatments the phages grew on the P. agglomerans carrier for 2 to 3 d after treatment application. The phages then grew preferentially on the pathogen, once it was introduced into this blossom ecosystem. The efficacy of the successful phage-based treatnlents was statistically similar to that of streptomycin, which is the most effective bactericide currently available for fire blight prevention.
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The in planta behaviour of amylovora was compared to that of Erwinia pyrifoliae, a closely related species that causes fire blight-like synlptoms on pears in southeast Asia. Duplex real-time PCR was used to monitor the population dynamics of both species on single blossonls. E. amylovora exhibited a greater competitive fitness on Bartlett pear blossoms than E. pyrifoliae. The genome of Erwinia phage <l>Ea21-4 was sequenced and annotated. Most of the 8-4.7 kB genome is substantially different from previously described sequences, though some regions are notably similar to Salmonella phage Felix 01 . Putative functions were assigned to approximately 30% of the predicted open reading frames based on amino acid sequence comparisons and N-terminal sequencing of structural proteins.   
Made available in DSpace on 2009-05-28T16:39:34Z (GMT). No. of bitstreams: 1 developmentofaba00lehmuoft.pdf: 24815096 bytes, checksum: 88d1f3afcd929cc248835d223ec63b9b (MD5)
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http://dr.library.brocku.ca/handle/10464/2238

Love Me Love My Phages - - Bacteriophages - The New Antibiotics - Part 3

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Company Develops Natural Way to Fight E. coli




BY COOKSON BEECHER | MAR 22, 2011


 


In the ongoing battle to keep the potentially deadly E. coli O157:H7 pathogen out of hamburger, a range of "killer strategies" has been proposed, among them: zap the meat with irradiation, test the hell out of it, check every carcass for surface contamination, and vaccinate every beef cow against E. coli.




 


(Stylised Phage)


 


Now comes an "all-natural" strategy -- one that recently received a thumbs-up from the U.S. Food and Drug Administration when the agency granted Baltimore-based Intralytix regulatory clearance for its phage-based EcoShield, which can significantly reduce or eliminate E. Coli O157:H7 in ground meat.


 


Intralytix CEO John Woloszyn told Food Safety News that while EcoShield is not a "silver bullet" for vanquishing E. coli, it does offer a "kill step" that can substantially reduce or eliminate E. coli O157:H7 by 99 to 100 percent.

He also said that getting the FDA clearance for the product "required a great deal of data and backup for its safety and effectiveness."

A blend of three phages, EcoShield is harmless to humans, animals and plants, but provides broad protection against E. coli O157:H7.

What are phages?

Also known as bacteriophages, phages are naturally occurring viruses that can be very effective in killing bacteria. They are everywhere --  inside of us, on our skin, in the soil, inside and on the outside of plants and animals, and even in the ocean. They go after specific targeted bacteria, infecting and then killing them.

Before the advent of antibiotics, phage therapy was used against a range of human diseases with varying results. With the growth of antibiotic resistance, it is now being viewed as an alternative to antibiotics, in some cases.

Intralytix has produced a short, easty-to-understand video that shows how phages work against foodborne pathogens.
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Revolutionary

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Woloszyn described using phages against foodborne pathogens as "revolutionary," pointing out that it's an "all-natural approach toward food safety."



"Most thinking in the Western World is that you need to use harsh chemicals or irradiation against pathogens instead of the powers of Mother Nature," he said, adding that consumers are increasingly looking for "natural" food products.



Woloszyn said that phages provide "an all-natural, nontoxic, safe and effective means for significantly reducing or eliminating disease-causing bacteria that are sometimes present on foods.


"Making food safer nature's way"  is a company slogan.



Looking ahead, Woloszyn said the company expects that "EcoShield will become a very important tool to make ground red meat safer."



Describing other advantages of the product, Woloszyn said that unlike irradiation, EcoShield doesn't affect color, taste or odor. It also meets Kosher and Halal certification requirements. And on the organic front, it's OMRI-listed, which means the Organic Materials Review Institute approves its use in organic production.

"Making food safer nature's way"  is a company slogan.



Looking ahead, Woloszyn said the company expects that "EcoShield will become a very important tool to make ground red meat safer."



Describing other advantages of the product, Woloszyn said that unlike irradiation, EcoShield doesn't affect color, taste or odor. It also meets Kosher and Halal certification requirements. And on the organic front, it's OMRI-listed, which means the Organic Materials Review Institute approves its use in organic production.



The problem with that, of course, is that many people like their hamburgers medium rare or rare, which means E. coli could be lurking inside of the burger.  Then, too, beef trim, which can be anything from meat pieces to exterior fat cut from steaks and other cuts, adds its own risks to the equation. Sometimes the trim is mixed into a slurry and doused with ammonia to clean it -- a product dubbed "pink slime." Beef trim is often added to hamburgers to keep costs down to consumers.



In 2009, Congresswoman Rosa DeLauro (D-CT) was worried enough about beef trim that she asked the USDA's Office of the Inspector General (OIG) to launch an investigation of how beef is tested.



Specifically, she asked the Inspector General to look into the scientific merits and identify any shortcomings of  USDA's N-60 testing system for beef.



The N-60 system requires USDA's Food Safety and Inspection Service to remove 60 pieces of product from a lot so they can be tested for pathogens such as E. coli.



Earlier this month, the OIG  said that the USDA should thoroughly reevaluate the program, pointing out that the sample size and design might not do a good enough job of detecting O157:H7 in beef trim.



The OIG also recommended that the USDA move to an inspection system that will determine which processing plants are at a higher risk of E. coli O157:H7.



The report is Phase 1 of OIG's response to a Congressional request to evaluate the N-60 program. In Phase II, OIG will look at the way testing is done at plants.



Early this month, USDA Inspector General Phyllis Fong "woke up" a few people during her presentation before a congressional subcommittee when she said that the N-60 testing program wasn't working.



She told the subcommittee members that a recently completed audit assessing how the Food Safety Inspection Service samples beef trim for E. coli revealed that the procedure "does not yield a statistical precision that is reasonable for food safety."



At the same time, she said that while 60 samples might be enough to detect widespread contamination, more are needed when E. coli is less prevalent.



Some beef-industry reps railed at that, saying that the more they do to eradicate E. coli from ground beef, the more testing the government wants to do.



One exasperated industry representative said the solution is simple enough: "Ban hamburgers."

  

On March 18, USDA Under Secretary for Food Safety Elisabeth Hagen told participants at the North American Meat Processors' Management Conference that the agency will probably call for increased testing of  beef trim and ground beef beyond the current N-60 sample rate, based on the OIG report.



But she also said that the USDA realizes that it can't "test its way to food safety" and that even if it took 500 samples from a lot, it would be impossible to find every pathogen in every lot.


Some meat-industry reps propose that E. coli prevention be directed to sampling beef carcasses since that's where E. coli is. They say that waiting to take samples until after the carcass is made into interior and exterior cuts doesn't make any sense. If, instead, standardized 'lot' samplings were performed on the exterior of carcasses, results could be available before the carcasses left the cooler, thus reducing the likelihood that contamination would ever reach the processing floor.



But Intralytix CEO Woloszyn said that each meat-processing plant has its own procedures and therefore needs to craft a food-safety plan that matches its own operation  He pointed out that beef trim often falls on the floor or is handled by workers or comes into contact with equipment that might be harboring E. coli.



"Often the best time to use EcoShield would be just before the meat is ground," he said.



EcoShield is applied in a very fine mist sprayed onto the meat. When necessary, the beef trim is rolled to make sure the mist covers all parts of the pieces of meat.



Woloszyn said it's easy to apply the product and applications don't require expensive equipment -- either a spray box or battery operated spray bottles.  



As for cost, he didn't supply a specific amount but said that it depends on how a processing plant is set up and what food-safety procedures it uses.



"We estimate the cost for each customer," he said. "We think the cost is very competitive especially when some steps a plant is taking can be eliminated when EcoShield is used."



Looking ahead



While the company doesn't yet have any customers for EcoShield, Woloszyn said some potential customers "are looking very seriously at this product."   "We're very hopeful about it," he said.



In an email to Food Safety News, Michael Martin, spokesman for meat-giant Cargill, said that while FDA approval for use of EcoShield is "an encouraging development," USDA has not approved it for use with meat products.

"Should USDA approval take place, Cargill would review the potential benefits of using EcoShield, just as we do with any measures that show promise and could potentially be added to our toolbox of food safety interventions," Martin said.
The FDA and USDA's Food Safety and Inspection Service (FSIS) work collaboratively on approvals of substances to be used in or on meat and poultry products. FSIS spokesman Neil Gaffney said the FDA has forwarded EcoShield's request to FSIS and the submission is currently under review as a safe and suitable treatment for meat by the FSIS Office of Policy and Program Development's Risk and Innovations Management Division.

"The review occurs simultaneously, with the intent to complete it within 2 months," Gaffney said.

More phage weapons
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In addition to EcoShield, Intralytix has another phage-based food-safety product, ListShield, which provides broad protection specifically against Listeria monocytogenes. According to the company's website, the product significantly reduces contamination levels of various foods by 99 to 100 percent. It can also be used on surfaces in food processing facilities and other establishments.

ListShield is FDA- and USDA-approved for direct applications on food.

The company has another phage-based product in the works, SalmShield, which targets selected, highly pathogenic Salmonella-serotypes in foods and food processing facilities.

In addition to bacteriophage-based food-safety products, Introlytix also focuses on the production and marketing of phage products to control bacterial pathogens in medical settings and the environmental.

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Sputnik virophage

http://en.wikipedia.org/wiki/Sputnik_virophage

From Wikipedia, the free encyclopedia 

Sputnik virophage    
Virus classification   
Group: Group I (dsDNA)   
Order: Unassigned   
Family: Unassigned   
Genus: Unassigned   
Species: Sputnik Virophage  

The Sputnik virophage (from "virus" and Greek φάγειν phagein "to eat") has a functional similarity with a bacteriophage. It is an icosahedral subviral agent that is 50 nanometres in size.[1] Sputnik has been found to multiply inside of an Amoeba, although the conditions for this are rather unusual. The Subviral agent is unable to multiply itself inside of the host cell on its own, but when the host cell has been infected sputnik harnesses the viral proteins to rapidly produce new copies of itself. Sputnik has a circular double stranded DNA genome which contains genes able to infect all three domains of life: Eukarya, Archaea and Bacteria. It is associated with the mamavirus, which presumably is related to Acanthamoeba polyphaga mimivirus (APMV). The mimivirus is a giant in the viral world; it has more genes than many bacteria and performs functions that normally occur only in cellular organisms. The mamavirus is even larger than the mimivirus, but the two are very similar in that they form large viral factories and complex viral particles.[2] Virophage growth is deleterious to APMV and results in the production of abortive forms and abnormal capsid assembly of APMV. In one of the experiments done by inoculating A.polyphaga with water containing an original strain of APMV, it was discovered that several capsid layers accumulate unsymmetrically on one side of the viral particle causing the virus to become ineffective. Sputnik decreased the yield of infective viral particle by 70% and also reduced the amoeba lysis by threefold at 24h.[1]

Of the twenty-one predicted protein-coding genes, three are apparently derived from APMV itself, one is a homologue of an archaeal virus, and four others are homologues of proteins in bacteriophages and eukaryotic viruses. Thirteen are ORFans, that is they do not have any detectable homologues in current sequence databases. The Sputnik has a high A + T content (73%) similar to that of APMV.

Several other homologues such as those of a primase–helicase, a packaging ATPase, an insertion sequence transposase DNA-binding subunit, and a Zn-ribbon protein, were detected in the Global Ocean Survey environmental data set, suggesting that virophages could be a currently unknown family of viruses. Considering its functional analogy with bacteriophages, this virus is classified as a virophage (ie a virus that infects other viruses).[3]

Sputnik was found to contain genes that were shared by the mimivirus. These genes could have been acquired by Sputnik after the association of APMV with the host and then interaction between the virophage and the viral host. Recombination within the viral factory might have resulted in the exchange of genes. Sputnik is one of the most convincing pieces of evidence for gene mixing and matching between viruses.

The presence of these genes homologous to the mimivirus in Sputnik suggests that gene transfer between Sputnik and the mimivirus can occur during the infection of Acanthamoeba. Therefore, it is hypothesized that the virophage could be a source of vehicle mediating lateral gene transfer between giant viruses, which constitute a significant part of the DNA virus population in the marine environments. Moreover, the presence of three APMV genes in Sputnik implies that gene transfer between a virophage and a giant virus is crucial to viral evolution.[4]

See also

Virus classification
Virusoid
Viroid
Virus
WikiSpecies:Virus
Satellite DNA, Minisatellite, Microsatellite (These should not be confused with Satellite (biology))

 References

^ a b Bernard La Scola, Christelle Desnues, Isabelle Pagnier, Catherine Robert, Lina Barrassi, Ghislain Fournous, Michèle Merchat, Marie Suzan-Monti, Patrick Forterre, Eugene Koonin and Didier Raoult (2008). "The virophage as a unique parasite of the giant mimivirus". Nature 454 (7205): 100. doi:10.1038/nature07218. PMID 18690211.

^ Xie, Yun. Sputnik the virophage: a virus gets a virus.ARS technica. Science Journal.

^ Scola , B. et al. 2008. The virophage as a unique parasite of the giant mimivirus. Nature 455, 100–104
^ http://google.com/search/cache?ei=UTF-8&p=virophage&y=Search&xa=fAH7qo6Dzk93kpVWXtGZ.A--%2C1228194443&fr=yfp-t-501&u=www.asm.org/microbe/index.asp%3Fbid%3D61386&w=virophage&d=PFqWc0fiR3Tw&icp=1&.intl=us

 External links
Viralzone: Sputnik virophage

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First 'virophage' could take the fight to viruses - health - 06 August 2008 - New Scientist


http://www.newscientist.com/article/dn14480-first-virophage-could-take-the-fight-to-viruses.html


'virophage' could take the fight to viruses 

18:00 06 August 2008 by Nic Fleming 

A newly discovered type of virus that spreads at the expense of other viruses, could be used to combat viral infections, say researchers.

Didier Raoult and colleagues from the University of the Mediterranean, France, say that the virus, called Sputnik, spreads by hijacking the replication machinery of the mamavirus - itself a new strain of the giant mimivirus.

The team says Sputnik is the first member of a new class they call "virophages" because of similarities with bacteriophages or phages - viruses that infect bacteria - and is the first time a virus has been seen to propagate at the expense of a viral host.

Research into phage therapy during the early 20th century was largely abandoned following the discovery of antibiotics.

Virus weapon?

Not only does Sputnik cut the spread of mamavirus in amoeba, Raoult's analysis also shows it has looted genes from other viruses. This could help researchers understand the genetic evolution of harmful viruses, and potentially, use virophages to destroy them. However, the team is cautious.

"It's too early to say we could use Sputnik as a weapon against big viruses or to modify them," says co-author Bernard La Scola, also at the University of the Mediterranean. "But phages are used to modify bacteria, so why not?"

Sputnik resembles satellite viruses - such as the one that causes hepatitis D. These can only replicate in and infect their host if another virus is present. A key difference, though, is that Sputnik significantly reduces the viral load of the other virus.

"What is interesting here is that Sputnik is doing this at the expense of the bigger virus," says Robin Weiss, of University College London.

However Geoffrey Smith, a virologist at Imperial College London, says this may not be surprising since both viruses are dependent upon the host cell for metabolites and will compete for them. He adds: "Bacteriophages replicate only in bacteria and that's all they need, so the use of the phrase 'virophage' is inappropriate."

Journal reference: Nature (DOI: 10.1038/nature07218)

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The "Bacteriophage" Journal
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Phages for Food safety Video
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Fire blight

From Wikipedia, the free encyclopedia

Fire blight - Wikipedia

https://en.wikipedia.org/wiki/Fire_blight
Fire blight, also written fireblight, is a contagious disease affecting apples, pears, and some other members of the family Rosaceae. It is a serious concern to apple and pear producers. Under optimal conditions, it can destroy an entire orchard in a single growing season.
The causal pathogen is Erwinia amylovora,[1] a Gram-negative bacterium in the family Enterobacteriaceae. Pears are the most susceptible, but apples, loquat, crabapples, quinces, hawthorn, cotoneaster, pyracantha, raspberry and some other rosaceous plants are also vulnerable. The disease is believed to be indigenous to North America, from where it spread to most of the rest of the world.
Fire blight is not believed to be present in Australia though it might possibly exist there.[2] It has been a major reason for a long-standing embargo on the importation of New Zealand apples to Australia.[3] Japan was likewise believed to be without the disease, but it was discovered in pears grown in northern Japan. Japanese authorities are, however, still denying its existence, and the Japanese scientist who discovered it is believed to have committed suicide after his name was leaked to affected farmers.[4] In Europe it is listed as a quarantine disease, and has been spreading along Hawthorn (Crataegus) hedges planted alongside railways, motorways and main roads.
                 
               
                                                         Erwinia amylovora
                                                        Scientific classification                                                        
Domain:Bacteria
Kingdom:Eubacteria
Phylum:Proteobacteria
Class:Gammaproteobacteria
Order:Enterobacteriales
Family:Enterobacteriaceae
Genus:Erwinia
Species:E. amylovora
Binomial name
Erwinia amylovora
(Burrill 1882) Winslow et al. 1920
Type strain = NCPPB 683
                                                      

History

In the early 1800s, E.amylovara was the first bacterium that could be used in experiments to demonstrate that it did indeed cause disease in plants. It is accepted that this destructive crop bacteria had initially originated in North America. Today, E.amylovara can currently be found in all the provinces of Canada, as well as in some parts of the United States of America; states include Alabama,California, Colorado, Connecticut, Georgia, Illinois, Maine, Maryland, Michigan, New York, North Carolina, Ohio, Oregon, Pennsylvania, Texas, Utah, Virginia, Washington, West Virginia and Wisconsin. Other American countries of its occurrence include but are not limited to Mexico and Bermuda. On the African continent, E.amylovora has been confirmed in Egypt.
It is believed that the pathogen was first introduced into Northern Europe through bacterial ooze from fruit containers in the 1950s[citation needed], imported from Northern America. During the 1950s-1960's, E.amylovora had spread through much of Northern Europe, yet leaving large areas of Germany and France seemingly untouched by the disease of which the bacteria causes a devastating disease known as "fireblight". This was short lived, as E.amylovora made its presence known when it was discovered in the later 1990s in Germany. Nonetheless by the 1980s the E.amylovora bacteria had been found in the Eastern Mediterranean, although its appearance in this region is thought to be an isolated appearance and not as a result of local transmission. Finally from the years 1995-1996 cases of fireblight had begun to be reported in countries such as Hungary, Romania, Northern Italy and Northern Spain.

Symptoms

Tissues affected by the symptoms of Erwinia amylovora include blossoms, fruits, shoots, and branches of apple (Pomoideae), pear, and many other rosaceous plants. All symptoms are above ground and are typically easy to recognize. Symptoms on blossoms include water soaking of the floral receptacle, ovary, and peduncles. This results in a dull, gray-green appearance at 1–2 weeks after petal fall, and eventually tissues will shrivel and turn black. The base of the blossom and young fruit show similar symptoms as infection spreads. Opaque white or amber colored droplets of bacterial ooze can be seen on the infected tissue when the environment is high in humidity. Shoots show similar symptoms but develop much more rapidly. A “Shepherd's Crook,” can be seen when the tip of the shoot wilts, diseased shoot leaves typically have blackening along the mid-vein and then die. In number, diseased shoots give the tree a blighted appearance. Initial infection of blossoms and shoots can spread to larger tree limbs. Branches will darken and become water soaked. Advanced infection develops cracks in bark and a sunken surface. Wood under the bark will become streaked with black discoloration. Immature fruit forms water-soaked lesions and later turned black. Bacterial ooze can be found on these lesions. Severe infections result in fruit turning entirely black and shriveling.[5] A primary inoculum of this disease is typically from cankers formed the season before. The factors that determine whether or not cankers become active are not well known, but it is thought that cankers found on larger tree limbs are more likely to become active. It is also thought that age may be a factor.[6]

Dissemination

Honeybees and other insects, birds, rain and wind can transmit the bacterium to susceptible tissue. Injured tissue is also highly susceptible to infection, including punctures and tears caused by plant-sucking or biting insects. Hailstorms can infect an entire orchard in a few minutes, and growers do not wait until symptoms appear, normally beginning control measures within a few hours.
Once deposited, the bacterium enters the plant through open stomata and causes blackened, necrotic lesions, which may also produce a viscous exudate. This bacteria-laden exudate can be distributed to other parts of the same plant or to susceptible areas of different plants by rain, birds or insects, causing secondary infections. The disease spreads most quickly during hot, wet weatherand is dormant in the winter when temperatures drop. Infected plant tissue contains viable bacteria, however, and will resume production of exudate upon the return of warm weather in the following spring. This exudate is then the source for new rounds of primary infections.
The pathogen spreads through the tree from the point of infection via the plant's vascular system, eventually reaching the roots and/or graft junction of the plant. Once the plant's roots are affected, the death of the plant often results. Over pruning and over fertilization (especially with nitrogen) can lead to watersprout and other midsummer growth that leave the tree more susceptible.
E. amylovora typically makes its entry into its host xylem or cortical parenchyma. It can also enter through stomata, lenticles and hydathodes. It is dispersed by rain and or insects naturally, but this mode of dispersal is very ineffective and can only be effective for local transmission of the pathogen. Aerosols are also suspected in playing a role in its transmission due to the detection of E.amylovora in Mediterranean regions. In composition the pathogen is composed of short rods with rounded ends made motile by many peritrichous flagellae. E.amylovara is a gram negative bacterium (as stated above).

Management

Spraying plants with streptomycin or injecting plants with oxytetracycline can prevent new infections. The widespread use of streptomycin spray has led to antibiotic resistance in some areas, such as California and Washington. Certainbiological controls consisting of beneficial bacteria or yeast can also prevent fire blight from infecting new trees. The only effective treatment for plants already infected is to prune off the affected branches and remove them from the area. Plants or trees should be inspected routinely for the appearance of new infections. The rest of the plant can be saved if the blighted wood is removed before the infection spreads to the roots.[7] There is no known cure; prevention is the key.[8]
E.amylovora needs to be destroyed externally, before it enters the cell. This is simply because once it enters the host, it spreads during the endophytic phase of pathogenesis. Once this happens external control methods become ineffective. The ideal control method is done by making use of copper and antibiotics on the external of the plant. This is the only effective method and it is indeed preventative. Currently it has been noted that E.amylovora has developed a resistant to the antibiotic streptomycin, as do most bacteria due to their flexible ability to transfer preferential genes promoting resistivity to certain antibiotics horizontally from species not even similar to it as all bacterium can.[9]
Phytosanitary measures have been employed as the best sanitary measures against E.amylovora dispersal. High risk countries are encouraged not to import susceptible plants of the pathogen into their territory because, once the bacteria becomes established in an area it is nearly impossible to eradicate. Nurseries and orchards in such regions are placed on strict phytosanitary surveillance measures and well-monitored. Imported and infected crops are destroyed as soon as they are noticed since the bacteria spreads very rapidly and eradication methods are usually costly and inefficient.

Importance

Besides the historical importance of being the first bacterium proven to be a plant pathogen, it is extremely economically important.[5] Control and loss costs are estimated approximately $100 million a year in the USA. Specifically, in Michigan in the year 2000, $42 million in losses is estimated because of the removal of about 400,000 apple trees.[10] Warm, humid, and wet weather in May resulted in this epidemic. While approximately $68 million is estimated in losses in Washington and northern Oregon. E. amylovora is spread all through the USA and worldwide causing severe damage. Although, it is unlikely to cause severe damage in northern Europe. As long as E. amylovora is not introduced to Central Asia where wild apple trees still grow, it will not modify any ecosystems. Biodiversity is not impacted either, as no plant species are threatened with extinction due to this pathogen. Growing pears in Emilia-Romagna in Italy is a traditional activity for some families, and fire blight threatens this tradition that has been passed down for several generations.[11] In southern Germany apple and pear trees have been a part of the landscape for a long time, and are difficult to protect. The decline of apple and pear trees from their landscape can be expensive to replace and could have a negative effect on tourism. In the long-run, fire blight is a very important factor of economy and society

Pathogenesis

Pathogenicity depends on many different factors such as the production of the siderophore desferrioxamine, metalloproteases, plasmids, and histone-like proteins. However, some essential factors of pathogenicity are variations in the synthesis of extracellular polysaccharides (EPS) and the mechanism of type III secretion system and its associated proteins.[12] EPS helps bacterial pathogens avoid plant defenses, “clog” the host’s vascular system, protect bacteria against desiccation and attach to both surfaces and one another. One EPS is amylovoran, a polymer of pentasaccharide repeating units. If a strain of E. amylovora can not produce amylovoran it is not pathogenic and can not spread in plants. Levan is another EPS, and a lack of it will slow development of symptoms. Type III secretion systems are used for exporting and delivering effector proteins into the cytosol of host plants. This system mainly consists of Hrc proteins. Motility is another major virulence factor.[13] Since E. amylovora is not an obligate biotroph, it is able to survive outside the host which allows it to spread in many ways such as rain.

References


    1. The World Today - Local apple producers say no to Kiwis' fruit 13/04/2010 - ABC AUSTRALIA

      http://www.abc.net.au/worldtoday/content/2010/s2871221.htm


  3.  Helm, Leslie; Eisenstodt, Gale (July 22, 1996). "Caught in the Cross Fire of Pacific Apple War"  Los Angeles Times. Retrieved August 9, 2010.
  4. ^ Jump up to:a b Johnson, Kenneth B. "Fire Blight of Apple and Pear." The American Phytopathological Society. The Plant Health Instructor, 2000. Web. 15 Nov. 2016.
  5. Jump up^ Beer, Steven V., and Norelli, John L. "Fire Blight Epidemiology: Factors Affecting Release of Erwinia Amylovora by Cankers." Phytopathology 77.9 (1977): 1119-125. Web. 15 Nov. 2016.
  6. For remaining references  go to:
  7.                                               https://en.wikipedia.org/wiki/Fire_blight
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  1. Phage therapy for plant disease control with a focus on fire blight

          Judit Kolozsvári Nagy, Lóránt Király, Ildikó Schwarczinger

*
Published Online: 2011-12-25 | DOI: https://doi.org/10.2478/s11535-011-0093-x


 Abstract

The concept of using bacteriophages (bacterial viruses) as biocontrol agents in pest management emerged shortly after their discovery. Although research on phage-based biopesticides temporarily stopped with the advent of antibiotics, the appearance of antibiotic resistant bacterial strains led to a renewed interest in phage therapy for control of plant diseases. In the past twenty years numerous successful experiments have been reported on bacteriophage-based biocontrol measures, and several comprehensive studies have recently been published discussing detailed results of phage application practices in pest management, mainly from North American authors. The present review focuses on bacteriophage-mediated control of fire blight (caused by Erwinia amylovora (Burill) Winslow et al.), the most devastating bacterial disease of pome fruits. Research results from North America are discussed along with recent data from European laboratories.
Keywords: Erwinia amylovora; Fire blight; Biological control; Bacteriophage; Phage therapy

1. Introduction

    Erwinia amylovora (Burill) Winslowet al.is the causative agent of fire blight, the most destructive   disease ofseveral species within the family Rosaceae. This enterobacterial phytopathogen is present in most apple-and pear-growing regions and causes considerable economic losses in orchards [1]. The pathogen primarily infects open blossoms in the spring when warm and humid weather promotes its growth and dispersal into the vascular system of the plant [2]. Infected tissues become wilted and often necrotic, and may eventually die [3]. The disease, originating from North America, was introduced to Europe in the 1950s [4 ]. In Hungary it was first found in 1996 in an apple orchard, where more than 40 000 trees had to be removed because of infection by this pathogen [5].

 At present, the control of fire blight is met with several difficulties, since the most effective protection method, i.e. the timed application of the antibiotic streptomycin to open blossoms, is banned in most European countries. Specific concerns about recently emerged streptomycin-resistant E. amylovora strains, along with the general trend of avoiding the use of antibiotics in agriculture, are  leading  to the development of alternative  control strategies

. In  past  years,  numerous  studies  approached  this problem via  the  application  of  a  range  of  promising  biological control methods. These included the use of antagonistic bacterial saprophytes [6-13], plant systemic acquired  resistance  (SAR)  inducers  [14-18],  and construction of transgenic plants resistant to E.amylovora by  biotechnological  methods  [19-21].  Further  studies on  fire  blight  using  biological  control  measures  were directed towards the use of yeast [11] or avirulent strains of E. amylovora  [22,23], the application of plant extracts and etheric oils [13,24.25], or the use of a new antibiotic produced by symbiotic bacteria of the entomopathogenic  nematodes Xenorhabdus  budapestiensis  Lengyel et  al . and X. szentirmaii  Lengyel et al. [26]. Another novel and promising method for controlling the fire blight disease could be the use of bacteriophages.

2. Short history of phage therapy
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Bacteriophages  or  phages  are  bacterial  viruses  that were discovered by Twort in 1915 and by d’Herelle in 1917,  who  independently  reported  on  filterable  and transmissible agents of bacterial lysis [27]. In spite of the promising early results of phage therapy, the discovery of  broad-spectrum  activity  antibiotics  in  the  1940s resulted in the decline of research controlling bacterial diseases with bacteriophages in the Western world [28]. However, during this period, phage therapy had been practiced mainly in human healthcare in some Eastern European countries [29,30].
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In recent times, the appearance of multi-resistant bacterial strains, as well as the lack of discovering new and  effective  antibiotics,  has  resulted  in  a  renewed interest in phage therapy in the field of medicine [29-31]. This led to the development of effective formulations like the IntestiPhage by the Eliava Institute in Georgia, which contains twenty-three different phages active against a wide range of enteric human bacteria [30].
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Several  factors  have  contributed  to  an  increased interest  in  developing  bacteriophage-based  disease control  methods  in  modern  agriculture,  such  as  the expanding  knowledge  based  on  successful  phage applications  in  medicine  [30,32,33],  the  appearance of  copper  and  antibiotic  resistant  bacterial  strains in  the  field  [34],  and  the  need  for  environmentally friendly pesticides. Bacteriophages were first found to be associated with plant pathogenic bacteria in 1924. 
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Mallmann and Hemstreet later demonstrated that the filtrate of decomposed cabbage inhibited the growth of Xanthomonas campestris  nspv. campestris  [35], and by 2005 the first phage-containing pesticide (AgriPhage™) was registered with the U.S. Environmental Protection Agency (http://www.omnilytics.com/products/agriphage).
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This  biopesticide  contains  phages  specifically  used for  control  of  bacterial  spot  and  bacterial  speck  of tomato  and  pepper  plants,  including  a  mixture  of wild-type  phages  and  host  range  mutant  phages  of Xanthomonas campestris  pv . vesicatoria  (Doidge) Dye and Pseudomonas syringae pv. tomato (Okabe) Young et al.  [31,36, Jackson, U.S. Patent No. 4828999, 1989].
→
2.1 Recent use of bacteriophages against plant pathogens
Recently, bacteriophages have been found to be effective for control of several phytobacteria [37] such as Erwinia spp., which cause bacterial soft rot [38] and fire blight on apple and pear [23,39,40], Xanthomonas spp., which cause bacterial spot of tomato [41,42], peach [43,44], geranium [36], citrus [45], walnut blight [46], leaf blight of onion [47] and citrus canker [45], Ralstonia solanacearum (Smith) Yabuuchi et al., which causes bacterial wilt of  tobacco [48], Pseudomonas spp., which causes bacterial blotch of mushrooms [49], and Streptomyces scabies Lambert & Loria, which causes potato scab [50]. In spite of this increasing research success, so far only one phage-based biopesticide (AgriPhage™) is commercially available for controlling plant pathogenic bacteria.

(http://www.omnilytics.com/products/agriphage).

3. Control of Erwinia amylovora by bacteriophages

3.1 Isolation of phages

The first step of developing a phage-based biopesticide is the isolation of bacteriophages specific to the target pathogen. Phages of E. amylovora may be isolated from soil surrounding the infected plant, and from the diseased plant tissue as well. Although, a number of researchers have previously isolated bacteriophages demonstrating the ability to lyse E. amylovora [51-53], the earliest and most complete suggestions for phage-mediated control of fire blight were made by Erskine [54], who isolated a phage from soil which lysed both an E. amylovora strain and a yellow saprophytic bacterium Pantoea agglomerans (Ewing & Fife) Gavini et al. (formerly Erwinia herbicola). Depending on whether one or multiple host bacterium isolates or species are used 
for phage isolation, one can obtain phages that are either host specific or display a wide host response range. Ritchie and Klos [55,56] used a single host strain for isolation of phages and reported that the tested E. amylovora phages isolated from aerial parts of apple trees had a narrow host range, as they were able to lyse only isolates of E. amylovora and the closely related 
saprophyte, P. agglomerans. On the other hand, Gill et al. [57] found that phages isolated using a mixture of multiple host strains had a broader host range. During our own investigations, we used several Hungarian E. amylovora strains for the isolation of phages (Schwarczinger and Kolozsvári Nagy, unpublished data). We found that these phage isolates have a much broader host range than well known American phage isolates (ФEa1h ФEa100, ФEa104 and ФEa116). In fact, these Hungarian phage isolates were capable of lysing not only Hungarian E. amylovora strains, but also those derived from other geographical areas. However, we found that other plant pathogenic 
bacteria distantly related to E. amylovora (Xanthomonas spp., Pseudomonas spp., Agrobacterium spp.) were not susceptible to these phages (Schwarczinger and Kolozsvári Nagy, unpublished data)

3.2 Phages combined with other microorganisms or applied as phage mixtures

Since the 1970s, more and more phages have been isolated and subsequently characterized in detail.  [54-61]. However, until recently, numerous efforts to control fire blight in orchards failed because phage populations declined in the absence of E. amylovora [23,56,58]. This problem can be solved in two different ways, either by using avirulent E. amylovora strains or saprotrophic bacteria. Tharaud et al. [22] and Schnabel et al. [23] suggested the use of avirulent E. amylovora 
mutants with bacteriophages to improve phage persistence in the phyllosphere, thereby achieving 
reliable control efficacy, but this would carry the risk of reversion to virulence. Lehman [40] was the first to report successful application of broad host range E. amylovora bacteriophages in combination with phage carrier P. agglomerans to maintain a replicating phage population on blossom surfaces during the primary infection period, and limit the period of time that free phages were exposed to harmful sunlight [37]. Results of early studies focusing on the isolation and morphological characterization of phages within a single-phage model [51,62] allowed the estab-lishment of successful experiments from the 1990s onwards. Schnabel et al. [23] demonstrated the advantage of application of phage mixtures for improving control efficacy (for a discussion see the section “Evaluation of phage effects”).

[54-61]. However, until recently, numerous efforts to control fire blight in orchards failed because phage populations declined in the absence of E. amylovora [23,56,58]. This problem can be solved in two different ways, either by using avirulent E. amylovora strains or saprotrophic bacteria. Tharaud et al. [22] and Schnabel et al. [23] suggested the use of avirulent E. amylovora mutants with bacteriophages to improve phage persistence in the phyllosphere, thereby achieving reliable control efficacy, but this would carry the risk of reversion to virulence. Lehman [40] was the first 
to report successful application of broad host range E. amylovora bacteriophages in combination with phage carrier P. agglomerans to maintain a replicating phage population on blossom surfaces during the primary infection period, and limit the period of time that free phages were exposed to harmful sunlight [37]. Results of early studies focusing on the isolation and morphological characterization of phages within a single-phage model [51,62] allowed the establishment of successful experiments from the 1990s onwards. Schnabel et al. [23] demonstrated the advantage of application of phage mixtures for improving control efficacy (for a discussion see the section “Evaluation of phage effects”).

3.3 Time of treatment

The control efficacy of phages strongly depends on the timing of their application. Erskine [54] demonstrated in an experiment with pear slices that disease symptoms were prevented when E. amylovora and the lysogenic form of the saprophyte P. agglomerans were inoculated together. In another early study, Ritchie [62] observed decreased disease symptoms on apple seedlings when 
the ФEa1 phage and E. amylovora were inoculated at the same time. Schnabel et al. [23] noticed that following simultaneous application of the phage mixture and the bacterial pathogen, E. amylovora populations were significantly reduced. In contrast, reduction of fire blight was not significant when phages were applied a day before bacterial inoculation, since phage populations remained high only in the presence of the bacterial pathogen.

3.4 Evaluation of phage effects

Effects of phages on their bacterial hosts can be studied on immature pear slices and on apple or pear blossoms by use of the so-called drop test in liquid culture. Among these, the blossom assay is the best method to select the most effective phage candidates for biocontrol, because the main strategy for controlling fire blight with biocontrol agents is preventing the accumulation of E. amylovora populations on nutrient-rich stigmatic surfaces of blossoms in the spring [63,64].

Therefore, Svircev et al. [39] and Lehman [40] used a pear blossom model to determine the control effect of bacteriophages, as well as setting up initial parameters for field experiments and selecting the best phage isolates for orchard trials. To date Lehman has evaluated most extensively the effects of bacteriophages specific to E. amylovora. The author [40] conducted a
three-year field experiment in pear and apple orchards in Canada to study the efficacy of different phages on the blossoms of different cultivars of fruit trees. The evaluations included not only studies of the ability of  phages to suppress target bacterial populations, but also monitoring population dynamic changes of both the tested phages and a selected P. agglomerans strain 
(EH 21-5) which was used as a phage carrier. Results of multiplex real time PCR monitoring showed that phages multiplied in P. agglomerans for two to three days after biopesticide application, though they preferred the pathogen once it was introduced into the examined 
ecosystem [40]. Meanwhile, on four-year-old Gala apple trees, the average population of the bacterial pathogen was significantly reduced by approximately 50% to pre-experiment epiphytic levels, exhibiting a control efficacy statistically similar to that of streptomycin. This model system for the biocontrol of E. amylovora has a great advantage compared to other assays involving 
inoculation of immature pear fruit tissue [65], because it mimics the primary host infection pathway under conditions where a phage biopesticide is expected to work [66].

 Schnabel et al. [58] pointed to the advantages of using phage mixtures in controlling fire blight. They tested three E. amylovora-specific bacteriophage isolates in liquid culture, and found that individual phages (ΦEa1, ΦEa7, ΦEa116C) were slightly effective at controlling the growth of E. amylovora strain Ea110 in liquid culture, but the mixture of the three phages in different combinations reduced the bacterial populations by about 99% when applied at 104 PFU/ml. Furthermore, Schnabel et al. [23] inoculated apple blossoms in the field with a mixture of phages (ΦEa1, ΦEa116B, ΦEa116C), and counted healthy and symptomatic blossom clusters fifteen and twenty-two days after inoculation. There was a significant disease reduction observed on 
blossoms. Application of phage treatments one day after E. amylovora inoculation resulted in a less effective suppression of the pathogen compared to simultaneous inoculation and phage application. Applying phage treatments one day after Ea110 inoculation, the number of E. amylovora-infected blossom clusters was reduced by 26% and 17.2% at fifteen and twenty-two days after inoculation, respectively. However, applying Ea110 and the phage mixture together, the incidence of fire blight was reduced by 37% and 31% at fifteen and twenty-two 
days after inoculation, respectively.

 Schwarczinger et al. [67] used the blossom assay as well. They wanted to know whether the elimination effect of phages on E. amylovora populations depends on the test plants’ susceptibility to the pathogen. They found that the two selected bacteriophage isolates significantly reduced the number of bacteria re-isolated from flowers by at least 45% compared to the controls on all of the three investigated apple cultivars displaying different susceptibility to E. amylovora (Figure 1). The best results were obtained on the moderately resistant apple cultivar Freedom, where the phage H6 reduced the number of re-isolated bacteria by 90%. It can be concluded that the bacteriophages used in this study (H6 and H5B) are highly efficient in eliminating E. amylovora 
on apple flowers, especially in a moderately resistant apple cultivar under in vitro conditions.

 Schwarczinger and Kolozsvári Nagy (unpublished data) studied the biocontrol effects of Hungarian phage isolates in mixture on four ornamental plants (Pyracantha angustifolia (Franch.) Schneid., Cotoneaster horizontalis Decne., Sorbus domestica L. and Crataegus monogyna Jacq., Figure 2). For all four plant species, the application of phages in mixture provided a better biocontrol effect 
than individual applications; however, in most cases there were no significant differences in efficacy between the most effective phage (Φ-EaH2A) and the phage cocktail (Schwarczinger and Nagy, unpublished data). The best suppression effect was obtained on phage cocktail-treated P. angustifolia where necrosis was not observed on flowers even four days after inoculation. 

 In contrast, treatment with the phage mixture did not significantly reduce flower necrosis on S. domestica and C. monogyna (reduction of symptoms ranged from 12% and 28%). Infection rates of untreated controls indicated that the treated Sorbus and Crataegus species are much more susceptible to E. amylovora than the Pyracantha, and the Cotoneaster plants. Such an increased susceptibility to bacterial infection could explain the inefficiency of phages on the plant species 
mentioned above.It is extremely difficult to compare results of independent experiments on the effect of bacteriophages on E. amylovora. These experiments differ in several parameters including phage concentrations, the timing of bacterial inoculations, and phage treatments or 
application of phages either alone or in mixture with or without carrier microorganisms. 

 Furthermore, in most published experiments no positive controls, i.e. streptomycin or commercial biological control products, have been used. Table 1 summarizes the suppressive effects of several biocontrol agents on E. amylovora infection. Based on the presented data it is obvious that the efficacy of commercialized, bacteria-based biocontrol agents is lower than that of streptomycin. 
However, when the efficacy of the given biocontrol agent exceeded 55%, no streptomycin control was included (based on data of Table 1). According to our knowledge only Lehman [40] reported on studies where the efficacy of different phage + carrier (P. agglomerans EH21-5) combinations was compared to that of other commercial biocontrol products (BlightBan®A506, BlightBan®C9-1). 

 The author observed that two phage + carrier combinations (ΦEa21-4 + EH 21-5 and ΦEa46-1 + EH 21-5) and the streptomycin control had similarly reduced the incidence of E. amylovora by 50%, and 63%, respectively. However, it is worth mentioning that the application of BlightBan®C9-1 by itself gave a similar result.

 3.5 Molecular characterization of phages

As mentioned above, one of the main hurdles of successfully controlling bacterial diseases with
bacteriophages is the risk of evolution of phageresistant bacterium strains. Roach et al. [71] studied phage resistance by Dualplex real-time PCR to fnd out whether it is induced by the development of prophages or mutations within the bacterium. Prophages were detected in twenty-four of the twenty-seven phageresistant Ea110 isolates, thus lysogeny was responsible for their resistance. On the contrary, there were no detectable prophages in any of the six Ea29-7 phageresistant isolates; therefore, in this case resistance was thought to be the result of bacterial mutation. Based on early studies [54,55] it has been shown that the virulence of E. amylovora is attenuated in phageresistant bacteria. A similar phenomenon was also reported for Pseudomonas morsprunorum (Wormald) Yong et al. [72]. Roach et al. evaluated the role of bacterial exopolysaccharides (EPS) in phage resistance [73]. The authors found that increased EPS production led to higher propagation rates of bacteriophage  populations, while mutants defcient in amylovoran were resistant to bacteriophage attack. The results discussed above point to the importance of clarifying the genetic background of these bacterial viruses. To date, several comprehensive studies have been carried out that focus on the molecular characterization of a wide range of E. amylovora bacteriophage isolates. The frst such study evaluating the diversity of E. amylovora phages collected from soil samples and shoots of fre blight-infected apple, pear, and raspberry tissues was conducted by Schnabel and Jones [58].  

PLEASE NOTE: This is not the complete article, but gives some interesting ideas. For more information, use URL below. Click on Open Access PDF file, which will give complete Paper with illustrations. 



https://www.degruyter.com/view/j/biol.2012.7.issue-1/s11535-011-0093-x/s11535-011-0093-x.xml

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J Alzheimers Dis. 2008 Oct;15(2):193-8.


https://www.ncbi.nlm.nih.gov/pubmed/26869319

Filamentous bacteriophage as a novel therapeutic tool for Alzheimer's disease treatment.

Solomon B1.

Author information

Abstract

Antibodies towards the N-terminal region of the amyloid-beta peptide (AbetaP) bind to Abeta fibrils, leading to their disaggregation. We developed an immunization procedure using filamentous phages displaying the only four amino acids EFRH encompassing amino acids 3-6 of the 42 residues of AbetaP, found to be the main regulatory site for Abeta formation. Phages displaying EFRH epitope are effective in eliciting humoral response against AbetaP which, in turn, relieves amyloid burden in brains of amyloid-beta protein precursor transgenic mice, improving their ability to perform cognitive tasks. In order to overcome the low permeability of the blood brain barrier for targeting 'anti-aggregating' monoclonal antibodies (mAbs) to Abeta plaques in the brain, we applied antibody engineering methods to minimize the size of mAbs while maintaining their biological activity. Single-chain antibodies displayed on the surface of filamentous phage showed the ability to enter the central nervous system (CNS). The genetically engineered filamentous bacteriophage proved to be an efficient, nontoxic viral delivery vector to the brain, offering an obvious advantage over other mammalian vectors. The feasibility of these novel strategies for production and targeting of anti-aggregating antibodies against Abeta plaques to disease affected regions in the CNS may have clinical potential for treatment of Alzheimer's disease.
PMID:
18953108                                  
   
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 Gene. 2016 Jun 1;583(2):85-89. doi: 10.1016/j.gene.2016.02.005. Epub 2016 Feb 8.

https://www.ncbi.nlm.nih.gov/pubmed/26869319

Phage M13 for the treatment of Alzheimer and Parkinson disease.

Author information

Abstract

The studies of microbes have been instrumental in combatting infectious diseases, but they have also led to great insights into basic biological mechanism like DNA replication, transcription, and translation of mRNA. In particular, the studies of bacterial viruses, also called bacteriophage, have been quite useful to study specific cellular processes because of the ease to isolate their DNA, mRNA, and proteins. Here, I review the recent discovery of how properties of the filamentous phage M13 emerge as a novel approach to combat neurodegenerative diseases.

KEYWORDS:

Alzheimer disease; Bacteriophage M13; Parkinson disease
PMID:
26869319
DOI:
                           ..................................

Neurophage Pharma may be able to treat  Alzheimers, Parkinsons, Huntingtons and other brain diseases

brian wang            March 31 2016

Israeli scientist named Beka Solomon, a professor at Tel Aviv University, made a serendipitous discovery one day when she was testing a new class of agents against Alzheimer’s disease. If it pans out, it might mark the beginning of the end of Alzheimer’s, Parkinson’s, and many other neurodegenerative diseases. It’s a remarkable story, and the main character isn’t Solomon or any other scientist but a humble virus that scientists refer to as M13.

 Among the many varieties of viruses, there is a kind that only infects bacteria. Known as bacteriophages, or just phages, these microbes are ancient (over three billion years old) and ubiquitous: they’re found everywhere from the ocean floor to human stomachs. The phage M13’s goal is to infect just one type of bacteria, Escherichia coli, or E. coli, which can be found in copious amounts in the intestines of mammals. Like other microorganisms, phages such as M13 have only one purpose: to pass on their genes. In order to do this, they have developed weapons to enable them to invade, take over, and even kill their bacterial hosts. Before the advent of antibiotics, in fact, doctors occasionally used phages to fight otherwise incurable bacterial infections.
Neurophage Pharmaceuticals is a company formed around using the key proteins of the M13 virus to treat disease.

M13 phage-treated mice had 80% fewer plaques than untreated ones.
They were able to show the M13 phage dissolved amyloid-beta plaques when the phage was delivered through the rodents’ nasal passages. Over the next two years, researchers at NeuroPhage discovered something totally unexpected: the M13 virus could also dissolve other amyloid aggregates—the tau tangles found in Alzheimer’s and also the amyloid plaques associated with other diseases, including alpha-synuclein (Parkinson’s), huntingtin (Huntington’s disease), and superoxide dismutase (amyotrophic lateral sclerosis). The phage even worked against the amyloids in prion diseases (a class that includes Creutzfeldt-Jakob disease). Fisher and his colleagues demonstrated this first in test tubes and then in a series of animal experiments. Astonishingly, the simple M13 virus appeared in principle to possess the properties of a “pan therapy,” a universal elixir of the kind the chemist Chris Dobson had imagined.

 The M13 phage’s special abilities involved a set of proteins displayed on the tip of the virus, called GP3.






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