Phages Could Help Solve Antibiotic Resistance
April 14, 2019 at 11:12 p.m.
By Max [email protected]
The name “bacteriophages” is derived from the ancient Greek "phagein," to devour. Their discovery may turn out to be one of the great medical findings of the past century.
According to the Food and Drug Administration (FDA), bacteriophages (phages) are defined as RNA or DNA viruses that infect bacteria without infecting mammalian or plant cells. Phages are present throughout the environment, and humans are routinely exposed to them at high levels through food and water without adverse effects.
Phages have become a focus of research in the battle against antibiotic resistance in the United States. Although not currently permitted here, phages are used in other countries as antibiotic therapy. Depending on the results of the clinical research, phages may eventually become the treatment of choice for cases where antibiotics fail, but there are a host of problems to be solved before that happens.
In February the FDA announced the first U.S. clinical trial of an intravenously administered bacteriophage therapy had been approved. The proposed phase 1 and 2 trial will evaluate the safety, tolerability and efficacy of an experimental treatment for patients with ventricular assist devices who have developed Staphylococcus aureus infections. These infections are typically very difficult to eradicate with conventional antibiotics.
Most phages have double-stranded DNA encapsulated into an icosahedral shell of protein attached to a tail. At the end of the tail there are proteins that attach to cells. A simple explanation is as follows: The virus particle with its protein and DNA first lands on the outside of the specific bacterial cell and injects its DNA into the cell. The DNA of the bacterial virus then takes over the cell and is converted into a virus factory. The bacterial cell dies and hundreds of virus particles are released.
Advantages and Disadvantages of Phage Therapy
The discovery of viruses that can infect and destroy bacteria was greeted with considerable optimism in the early 1900s. Despite the efforts of a number of investigators, their use was generally abandoned soon after the introduction of antibiotics in the 1940s.
Lytic phages, of course, are similar to antibiotics in that they have remarkable antibacterial activity and their theoretical advantages are good reasons for renewed interest. Earlier reported results using phages may have been even better if it had been recognized that there are many types of phages and that each is specific for a special host range of bacteria. This lack of understanding resulted in applications of phage growing on one bacterial host but with little, if any, ability to influence clinical infections caused by other bacterial strains.
Phages have a number of advantages compared to antibiotics. For one, phages usually affect only the targeted bacterial species. Anti-biotics target both pathogenic microorganisms and normal microflora. This affects the microbial balance in the patient which may lead to a serious secondary infection.
Second, phages replicate at the site of infection and are available where they are most needed. Antibiotics are metabolized, eliminated from the body and do not concentrate at the site of infection.
Third, phages are found throughout nature and it is easy to find new phages when bacteria become resistant to them. This means that selecting new phages is a relatively rapid process that can be accomplished in days or weeks, whereas developing an antibiotic is a time-consuming process that can take several years. Phages appear to be safe as no serious side effects have been described.
Phage therapy is not without disadvantages. There are no internationally recognized studies that attest to the efficacy of phages in human patients. There are a number of publications on phage therapy, but very few papers in which the pharmacokinetics of therapeutic phage preparations is described. Additional research would be needed to obtain the type of pharmacological and toxicological data required by the FDA. There is a paucity of appropriately conducted, placebo-controlled studies.
Because of the high specificity of phages, many negative results may have been obtained because of failure to select phages for the targeted bacterial species. Another concern regarding the therapeutic use of phages is that the development of resistance may hamper their effectiveness. Because bacteria are under constant threat of infection by phages, there are strong selective pressures to acquire resistance.
Phage therapy is not yet accepted in Western medicine. There still remain many important questions to address before phages can be endorsed for therapeutic use.
Max Sherman is a medical writer and pharmacist retired from the medical device industry. He has taught college courses on regulatory and compliance issues at Ivy Tech, Grace College and Butler University. Sherman has an unquenchable thirst for knowledge on all levels. Eclectic Science, the title of his column, touches on famed doctors and scientists, human senses, aging, various diseases, and little-known facts about many species, including their contributions to scientific research. He can be reached by email at [email protected].
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The name “bacteriophages” is derived from the ancient Greek "phagein," to devour. Their discovery may turn out to be one of the great medical findings of the past century.
According to the Food and Drug Administration (FDA), bacteriophages (phages) are defined as RNA or DNA viruses that infect bacteria without infecting mammalian or plant cells. Phages are present throughout the environment, and humans are routinely exposed to them at high levels through food and water without adverse effects.
Phages have become a focus of research in the battle against antibiotic resistance in the United States. Although not currently permitted here, phages are used in other countries as antibiotic therapy. Depending on the results of the clinical research, phages may eventually become the treatment of choice for cases where antibiotics fail, but there are a host of problems to be solved before that happens.
In February the FDA announced the first U.S. clinical trial of an intravenously administered bacteriophage therapy had been approved. The proposed phase 1 and 2 trial will evaluate the safety, tolerability and efficacy of an experimental treatment for patients with ventricular assist devices who have developed Staphylococcus aureus infections. These infections are typically very difficult to eradicate with conventional antibiotics.
Most phages have double-stranded DNA encapsulated into an icosahedral shell of protein attached to a tail. At the end of the tail there are proteins that attach to cells. A simple explanation is as follows: The virus particle with its protein and DNA first lands on the outside of the specific bacterial cell and injects its DNA into the cell. The DNA of the bacterial virus then takes over the cell and is converted into a virus factory. The bacterial cell dies and hundreds of virus particles are released.
Advantages and Disadvantages of Phage Therapy
The discovery of viruses that can infect and destroy bacteria was greeted with considerable optimism in the early 1900s. Despite the efforts of a number of investigators, their use was generally abandoned soon after the introduction of antibiotics in the 1940s.
Lytic phages, of course, are similar to antibiotics in that they have remarkable antibacterial activity and their theoretical advantages are good reasons for renewed interest. Earlier reported results using phages may have been even better if it had been recognized that there are many types of phages and that each is specific for a special host range of bacteria. This lack of understanding resulted in applications of phage growing on one bacterial host but with little, if any, ability to influence clinical infections caused by other bacterial strains.
Phages have a number of advantages compared to antibiotics. For one, phages usually affect only the targeted bacterial species. Anti-biotics target both pathogenic microorganisms and normal microflora. This affects the microbial balance in the patient which may lead to a serious secondary infection.
Second, phages replicate at the site of infection and are available where they are most needed. Antibiotics are metabolized, eliminated from the body and do not concentrate at the site of infection.
Third, phages are found throughout nature and it is easy to find new phages when bacteria become resistant to them. This means that selecting new phages is a relatively rapid process that can be accomplished in days or weeks, whereas developing an antibiotic is a time-consuming process that can take several years. Phages appear to be safe as no serious side effects have been described.
Phage therapy is not without disadvantages. There are no internationally recognized studies that attest to the efficacy of phages in human patients. There are a number of publications on phage therapy, but very few papers in which the pharmacokinetics of therapeutic phage preparations is described. Additional research would be needed to obtain the type of pharmacological and toxicological data required by the FDA. There is a paucity of appropriately conducted, placebo-controlled studies.
Because of the high specificity of phages, many negative results may have been obtained because of failure to select phages for the targeted bacterial species. Another concern regarding the therapeutic use of phages is that the development of resistance may hamper their effectiveness. Because bacteria are under constant threat of infection by phages, there are strong selective pressures to acquire resistance.
Phage therapy is not yet accepted in Western medicine. There still remain many important questions to address before phages can be endorsed for therapeutic use.
Max Sherman is a medical writer and pharmacist retired from the medical device industry. He has taught college courses on regulatory and compliance issues at Ivy Tech, Grace College and Butler University. Sherman has an unquenchable thirst for knowledge on all levels. Eclectic Science, the title of his column, touches on famed doctors and scientists, human senses, aging, various diseases, and little-known facts about many species, including their contributions to scientific research. He can be reached by email at [email protected].
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