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Phage renaissance: new hope against antibiotic resistance.

Potera C - Environ. Health Perspect. (2013)

View Article: PubMed Central - PubMed

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By comparison, he says, antibiotics and chemical disinfectants also kill good bacteria “like casualties of war. ” There’s an increasing recognition that we cannot kill all microbes, “and we don’t want to,” Sulakvelidze notes, “because without bacteria there would be no life on Earth. ” Intralytix’s ListShield™, the first phage product approved by the FDA as a food additive, targets Listeria monocytogenes in ready-to-eat meat and poultry (e.g., deli meats and frankfurters)... ListShield is sprayed on meat products as well as on drains, floors, coolers, and other surfaces that might harbor L. monocytogenes at food processing plants... According to Sulakvelidze, the product typically reduces L. monocytogenes contamination by 95% or better... Peptidases break down proteins, amidases break amide bonds, and lysozymes break down peptidoglycans found in cell walls of bacteria... Combined, they are more effective than any single approach alone... The treatment was proven safe, the main goal of phase 1 trials. “Before this, no formal study was ever done in the United States to show the safety of phage cocktails,” says Sulakvelidze... Although bacteria do develop resistance to their viral predators, several mutations must occur to beat all the phages in a cocktail. “The chance of bacteria becoming resistant to multiple phages in a cocktail simultaneously is very unlikely,” says Sharma. “Using multiple phages targeting the same pathogen in a cocktail provides a built-in contingency against development of phage resistance in bacteria. ” Sulakvelidze predicts that sometime in the future his company’s products will need to be updated with new phages... But while phages offer unprecedented flexibility to address bacterial resistance, phage cocktails require that large amounts of the viral workhorses be grown inside pathogenic bacteria in a laboratory, theoretically putting workers and the environment at risk... Taking advantage of lysins offers a safer alternative, according to Seal... When Intralytix sought FDA approval for its ListShield product “there were zero guidelines for us to follow, and it took four years,” says Sulakvelidze... The process was “mutually educational for us and the FDA, and we hope we cleared the way for others to follow,” Sulakvelidze says... Human phage therapies are regulated as drugs and biological products, and require an Investigational New Drug (IND) Application for testing in people... For traditional drugs, the FDA wants each component of a drug combination to be proven safe and effective both individually and in combination... It will take time to sort out the advan-tages and disadvantages of phages as well as the logistics of registering them with appropriate authorities... But phages’ proponents insist the benefits are worth it: Whether applied as cocktails, lysins, or individual phages, these agents offer the potential of a vast arsenal of new antibacterial agents.

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How Phages WorkAll known bacteria are thwarted by phages, which are extremely specific and only attack the strain of bacteria they evolved to inhabit and kill (mammalian and plant cells lack the receptors required for phage infection, so phages are harmless against them). Phages first attach to and puncture the bacterial membrane. Phage DNA is injected into the host cell. The host cell’s DNA transcription is suppressed, and phage-specific proteins are synthesized instead. New phages are assembled, the host cell membrane is disrupted, and large numbers of new phages are released from the host bacterium, which dies.22An estimated 1030–1032 phages exist in the biosphere,22 and an estimated 1023 phage infections occur per second.24 Every 48 hours, phages destroy about half the bacteria in the world,25,26 a dynamic process that occurs in all ecosystems.14,24Phages have infected bacteria for billions of years, and just as bacteria mutate to resist drugs, they also mutate to render phages ineffective. However, new phages continually evolve against the mutated bacteria.27 “It’s an evolutionary arms race,” says Daniel Nelson of the University of Maryland’s Institute for Bioscience and Biotechnology Research. Because phages cannot reproduce on their own, they must infect bacteria, which, in turn, spend massive amounts of energy trying to avoid death by phage.However, phages are not totally bad and even offer bacteria a fitness advantage by transferring genes for antibiotic resistance and toxins to bacteria. To acquire desirable traits while avoiding death, bacteria use restriction modification systems to cut out deleterious phage DNA and keep beneficial phage DNA.27 “Nonetheless, phages adapt and evolve more rapidly than bacteria, so the cat-and-mouse game continues as both sides try to out-evolve each other,” says Nelson.© Medi-Mation Ltd/Science Source
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f2: How Phages WorkAll known bacteria are thwarted by phages, which are extremely specific and only attack the strain of bacteria they evolved to inhabit and kill (mammalian and plant cells lack the receptors required for phage infection, so phages are harmless against them). Phages first attach to and puncture the bacterial membrane. Phage DNA is injected into the host cell. The host cell’s DNA transcription is suppressed, and phage-specific proteins are synthesized instead. New phages are assembled, the host cell membrane is disrupted, and large numbers of new phages are released from the host bacterium, which dies.22An estimated 1030–1032 phages exist in the biosphere,22 and an estimated 1023 phage infections occur per second.24 Every 48 hours, phages destroy about half the bacteria in the world,25,26 a dynamic process that occurs in all ecosystems.14,24Phages have infected bacteria for billions of years, and just as bacteria mutate to resist drugs, they also mutate to render phages ineffective. However, new phages continually evolve against the mutated bacteria.27 “It’s an evolutionary arms race,” says Daniel Nelson of the University of Maryland’s Institute for Bioscience and Biotechnology Research. Because phages cannot reproduce on their own, they must infect bacteria, which, in turn, spend massive amounts of energy trying to avoid death by phage.However, phages are not totally bad and even offer bacteria a fitness advantage by transferring genes for antibiotic resistance and toxins to bacteria. To acquire desirable traits while avoiding death, bacteria use restriction modification systems to cut out deleterious phage DNA and keep beneficial phage DNA.27 “Nonetheless, phages adapt and evolve more rapidly than bacteria, so the cat-and-mouse game continues as both sides try to out-evolve each other,” says Nelson.© Medi-Mation Ltd/Science Source


Phage renaissance: new hope against antibiotic resistance.

Potera C - Environ. Health Perspect. (2013)

How Phages WorkAll known bacteria are thwarted by phages, which are extremely specific and only attack the strain of bacteria they evolved to inhabit and kill (mammalian and plant cells lack the receptors required for phage infection, so phages are harmless against them). Phages first attach to and puncture the bacterial membrane. Phage DNA is injected into the host cell. The host cell’s DNA transcription is suppressed, and phage-specific proteins are synthesized instead. New phages are assembled, the host cell membrane is disrupted, and large numbers of new phages are released from the host bacterium, which dies.22An estimated 1030–1032 phages exist in the biosphere,22 and an estimated 1023 phage infections occur per second.24 Every 48 hours, phages destroy about half the bacteria in the world,25,26 a dynamic process that occurs in all ecosystems.14,24Phages have infected bacteria for billions of years, and just as bacteria mutate to resist drugs, they also mutate to render phages ineffective. However, new phages continually evolve against the mutated bacteria.27 “It’s an evolutionary arms race,” says Daniel Nelson of the University of Maryland’s Institute for Bioscience and Biotechnology Research. Because phages cannot reproduce on their own, they must infect bacteria, which, in turn, spend massive amounts of energy trying to avoid death by phage.However, phages are not totally bad and even offer bacteria a fitness advantage by transferring genes for antibiotic resistance and toxins to bacteria. To acquire desirable traits while avoiding death, bacteria use restriction modification systems to cut out deleterious phage DNA and keep beneficial phage DNA.27 “Nonetheless, phages adapt and evolve more rapidly than bacteria, so the cat-and-mouse game continues as both sides try to out-evolve each other,” says Nelson.© Medi-Mation Ltd/Science Source
© Copyright Policy - public-domain
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3569700&req=5

f2: How Phages WorkAll known bacteria are thwarted by phages, which are extremely specific and only attack the strain of bacteria they evolved to inhabit and kill (mammalian and plant cells lack the receptors required for phage infection, so phages are harmless against them). Phages first attach to and puncture the bacterial membrane. Phage DNA is injected into the host cell. The host cell’s DNA transcription is suppressed, and phage-specific proteins are synthesized instead. New phages are assembled, the host cell membrane is disrupted, and large numbers of new phages are released from the host bacterium, which dies.22An estimated 1030–1032 phages exist in the biosphere,22 and an estimated 1023 phage infections occur per second.24 Every 48 hours, phages destroy about half the bacteria in the world,25,26 a dynamic process that occurs in all ecosystems.14,24Phages have infected bacteria for billions of years, and just as bacteria mutate to resist drugs, they also mutate to render phages ineffective. However, new phages continually evolve against the mutated bacteria.27 “It’s an evolutionary arms race,” says Daniel Nelson of the University of Maryland’s Institute for Bioscience and Biotechnology Research. Because phages cannot reproduce on their own, they must infect bacteria, which, in turn, spend massive amounts of energy trying to avoid death by phage.However, phages are not totally bad and even offer bacteria a fitness advantage by transferring genes for antibiotic resistance and toxins to bacteria. To acquire desirable traits while avoiding death, bacteria use restriction modification systems to cut out deleterious phage DNA and keep beneficial phage DNA.27 “Nonetheless, phages adapt and evolve more rapidly than bacteria, so the cat-and-mouse game continues as both sides try to out-evolve each other,” says Nelson.© Medi-Mation Ltd/Science Source

View Article: PubMed Central - PubMed

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

By comparison, he says, antibiotics and chemical disinfectants also kill good bacteria “like casualties of war. ” There’s an increasing recognition that we cannot kill all microbes, “and we don’t want to,” Sulakvelidze notes, “because without bacteria there would be no life on Earth. ” Intralytix’s ListShield™, the first phage product approved by the FDA as a food additive, targets Listeria monocytogenes in ready-to-eat meat and poultry (e.g., deli meats and frankfurters)... ListShield is sprayed on meat products as well as on drains, floors, coolers, and other surfaces that might harbor L. monocytogenes at food processing plants... According to Sulakvelidze, the product typically reduces L. monocytogenes contamination by 95% or better... Peptidases break down proteins, amidases break amide bonds, and lysozymes break down peptidoglycans found in cell walls of bacteria... Combined, they are more effective than any single approach alone... The treatment was proven safe, the main goal of phase 1 trials. “Before this, no formal study was ever done in the United States to show the safety of phage cocktails,” says Sulakvelidze... Although bacteria do develop resistance to their viral predators, several mutations must occur to beat all the phages in a cocktail. “The chance of bacteria becoming resistant to multiple phages in a cocktail simultaneously is very unlikely,” says Sharma. “Using multiple phages targeting the same pathogen in a cocktail provides a built-in contingency against development of phage resistance in bacteria. ” Sulakvelidze predicts that sometime in the future his company’s products will need to be updated with new phages... But while phages offer unprecedented flexibility to address bacterial resistance, phage cocktails require that large amounts of the viral workhorses be grown inside pathogenic bacteria in a laboratory, theoretically putting workers and the environment at risk... Taking advantage of lysins offers a safer alternative, according to Seal... When Intralytix sought FDA approval for its ListShield product “there were zero guidelines for us to follow, and it took four years,” says Sulakvelidze... The process was “mutually educational for us and the FDA, and we hope we cleared the way for others to follow,” Sulakvelidze says... Human phage therapies are regulated as drugs and biological products, and require an Investigational New Drug (IND) Application for testing in people... For traditional drugs, the FDA wants each component of a drug combination to be proven safe and effective both individually and in combination... It will take time to sort out the advan-tages and disadvantages of phages as well as the logistics of registering them with appropriate authorities... But phages’ proponents insist the benefits are worth it: Whether applied as cocktails, lysins, or individual phages, these agents offer the potential of a vast arsenal of new antibacterial agents.

Show MeSH
Related in: MedlinePlus