Hurdles For Phage Therapy Pt To Become A Reality

Alternative treatment modes for antibiotic-resistant bacterial pathogens have become a public health priority. Bacteriophages are bacterial viruses that infect and lyse bacterial cells. Since bacteriophages are frequently bacterial host species-specific and can often also infect antibiotic-resistant bacterial cells, they could represent ideal antimicrobials for fighting the antibiotic resistance crisis. The medical use of bacteriophages has become known as phage therapy. It is widely used in Russia, where phage cocktails are sold in pharmacies as an over-the-counter drug. However, no phage product has been registered for medical purposes outside of the former Soviet Union. The current Special Issue of Viruses contains a collection of papers from opinion leaders in the field who explore hurdles to the introduction of phage therapy in western countries. The articles cover diverse topics ranging from patent to regulatory issues, the targeting of suitable bacterial infections, and the selection and characterization of safe and efficient phage cocktails. Phage resistance is discussed, and gaps in our knowledge of phage–bacterium interactions in the mammalian body are revealed, while other articles explore the use of phages in food production and processing.

Alternative treatment modes for antibiotic-resistant bacterial pathogens have become a public health priority. Bacteriophages are bacterial viruses that infect and lyse bacterial cells. Since bacteriophages are frequently bacterial host species-specific and can often also infect antibiotic-resistant bacterial cells, they could represent ideal antimicrobials for fighting the antibiotic resistance crisis. The medical use of bacteriophages has become known as phage therapy. It is widely used in Russia, where phage cocktails are sold in pharmacies as an over-the-counter drug. However, no phage product has been registered for medical purposes outside of the former Soviet Union. The current Special Issue of Viruses contains a collection of papers from opinion leaders in the field who explore hurdles to the introduction of phage therapy in western countries. The articles cover diverse topics ranging from patent to regulatory issues, the targeting of suitable bacterial infections, and the selection and characterization of safe and efficient phage cocktails. Phage resistance is discussed, and gaps in our knowledge of phage-bacterium interactions in the mammalian body are revealed, while other articles explore the use of phages in food production and processing.

Historically, the first observation of a transmissible lytic agent that is specifically active against a bacterium (Bacillus anthracis) was by a Russian microbiologist Nikolay Gamaleya in 1898. At that time, however, it was too early to make a connection to another discovery made by Dmitri Ivanovsky in 1892 and Martinus Beijerinck in 1898 on a non-bacterial pathogen infecting tobacco plants. Thus the viral world was discovered in two of the three domains of life, and our current understanding is that viruses represent the most abundant biological entities on the planet. The potential of bacteriophages for infection treatment have been recognized after the discoveries by Frederick Twort and Felix d’Hérelle in 1915 and 1917. Subsequent phage therapy developments, however, have been overshadowed by the remarkable success of antibiotics in infection control and treatment, and phage therapy research and development persisted mostly in the former Soviet Union countries, Russia and Georgia, as well as in France and Poland. The dramatic rise of antibiotic resistance and especially of multi-drug resistance among human and animal bacterial pathogens, however, challenged the position of antibiotics as a single most important pillar for infection control and treatment. Thus there is a renewed interest in phage therapy as a possible additive/alternative therapy, especially for the infections that resist routine antibiotic treatment. The basis for the revival of phage therapy is affected by a number of issues that need to be resolved before it can enter the arena, which is traditionally reserved for antibiotics. Probably the most important is the regulatory issue: How should phage therapy be regulated? Similarly to drugs? Then the co-evolving nature of phage-bacterial host relationship will be a major hurdle for the production of consistent phage formulae. Or should we resort to the phage products such as lysins and the corresponding engineered versions in order to have accurate and consistent delivery doses? We still have very limited knowledge about the pharmacodynamics of phage therapy. More data, obtained in animal models, are necessary to evaluate the phage therapy efficiency compared, for example, to antibiotics. Another aspect is the safety of phage therapy. How do phages interact with the immune system and to what costs, or benefits? What are the risks, in the course of phage therapy, of transduction of undesirable properties such as virulence or antibiotic resistance genes? How frequent is the development of bacterial host resistance during phage therapy? Understanding these and many other aspects of phage therapy, basic and applied, is the main subject of this Topic.

This Research Topic is dedicated to Prof. Elisabeth Kutter on the occasion of her 80th birthday. Dr. Kutter’s career as a phage scientist has extended nearly 60 years. She has been a pioneer as a woman in science. She started to work with phage at the University of Rochester, New York working with Dr. Wiberg on radioisotopes making excellent progress in the field – progress which was even cited in Luria’s 1969 Nobel Prize talk. Betty first encountered phage therapy during a visit to Georgia in 1990 which was part of a longer stay in the former Soviet Union under a US-USSR research exchange program. Dr. Kutter was one of the first Americans to advocate for phage therapy in the post antibiotic era. Betty started hosting the Evergreen International Phage meetings in Olympia, Washington, from 1975 onward, which helped to develop a strong phage community with participation increasing over the years to 350 at the 23 rd biannual last year. Betty continues to be an active member in the phage community, sharing her experience and working with all of us toward her ultimate goal of making phage therapy available worldwide thus reducing the burden caused by antibiotic resistant bacterial infections.

Practical Handbook of Microbiology, 4th edition provides basic, clear and concise knowledge and practical information about working with microorganisms. Useful to anyone interested in microbes, the book is intended to especially benefit four groups: trained microbiologists working within one specific area of microbiology; people with training in other disciplines, and use microorganisms as a tool or "chemical reagent"; business people evaluating investments in microbiology focused companies; and an emerging group, people in occupations and trades that might have limited training in microbiology, but who require specific practical information. Key Features Provides a comprehensive compendium of basic information on microorganisms—from classical microbiology to genomics. Includes coverage of disease-causing bacteria, bacterial viruses (phage), and the use of phage for treating diseases, and added coverage of extremophiles. Features comprehensive coverage of antimicrobial agents, including chapters on anti-fungals and anti-virals. Covers the Microbiome, gene editing with CRISPR, Parasites, Fungi, and Animal Viruses. Adds numerous chapters especially intended for professionals such as healthcare and industrial professionals, environmental scientists and ecologists, teachers, and businesspeople. Includes comprehensive survey table of Clinical, Commercial, and Research-Model bacteria. The Open Access version of this book, available at http://www.taylorfrancis.com, has been made available under a Creative Commons Attribution-Non Commercial-No Derivatives 4.0 license. Chapter 21, "Archaea," of this book is freely available as a downloadable Open Access PDF under a Creative Commons Attribution-Non Commercial-No Derivatives 4.0 license available at http://www.taylorfrancis.com See Emanuel Goldman's Open Access article: "Lamarck redux and other false arguments against SARS-CoV-2 vaccination," https://www.embopress.org/doi/full/10.15252/embr.202254675

This is the first book to systemize all levels of communicative behavior of phages. Phages represent the most diverse inhabitants on this planet. Until today they are completely underestimated in their number, skills and competences and still remain the dark matter of biology. Phages have serious effects on global energy and nutrient cycles. Phages actively compete for host. They can distinguish between ‘self’ and ‘non-self’ (complement same, preclude others). They process and evaluate available information and then modify their behaviour accordingly. These diverse competences show us that this capacity to evaluate information is possible owing to communication processes within phages (intra-organismic), between the same, related and different phage species (interorganismic), and between phages and non-phage organisms (transorganismic). This is crucial in coordinating infection strategies (lytic vs. lysogenic) and recombination in phage genomes. In 22 chapters, expert contributors review current research into the varying forms of phage biocommunication and Phagetherapy. Biocommunication of Phages aims to assess the current state of research, to orient further investigations on how phages communicate with each other to coordinate their behavioral patterns, and to inspire further investigation of the role of non-phage viruses (non-lytic, non-prokaryotic) in these highly dynamic interactional networks.

Our ability to treat common bacterial infections with antibiotics goes back only 65 years. However, the authors of this report make it clear that sustaining a supply of effective and affordable antibiotics cannot be without changes to the incentives facing patients, physicians, hospitals, insurers, and pharmaceutical manufacturers. In fact, increasing resistance to these drugs is already exacting a terrible price. Every day in the United States, approximately 172 men, women, and children die from infections caused by antibiotic-resistant bacteria in hospitals alone. Beyond those deaths, antibiotic resistance is costing billions of dollars through prolonged hospital stays and the need for doctors to resort to ever more costly drugs to use as substitute treatments. Extending the Cure presents the problem of antibiotic resistance as a conflict between individual decision makers and their short-term interest and the interest of society as a whole, in both present and future: The effort that doctors make to please each patient by prescribing a drug when it might not be properly indicated, poor monitoring of discharged patients to ensure that they do not transmit drug-resistant pathogens to other persons, excesses in the marketing of new antibiotics, and the broad overuse of antibiotics all contribute to the development and spread of antibiotic-resistant bacteria. The book explores a range of policy options that would encourage patients, health care providers, and managed care organizations to serve as more responsible stewards of existing antibiotics as well as proposals that would give pharmaceutical firms greater incentives to develop new antibiotics and avoid overselling. If the problem continues unaddressed, antibiotic resistance has the potential to derail the health care system and return us to a world where people of all ages routinely die from simple infections. As a basis for future research and a spur to a critically important dialogue, Extending the Cure is a fundamental first step in addressing this public health crisis. The Extending the Cure project is funded in part by the Robert Wood Johnson Foundation through its Pioneer Portfolio.

Humans coexist with millions of harmless microorganisms, but emerging diseases, resistance to antibiotics, and the threat of bioterrorism are forcing scientists to look for new ways to confront the microbes that do pose a danger. This report identifies innovative approaches to the development of antimicrobial drugs and vaccines based on a greater understanding of how the human immune system interacts with both good and bad microbes. The report concludes that the development of a single superdrug to fight all infectious agents is unrealistic.