Antibiotic Resistance: Nature to the Rescue with Bacteriophages

The threat that is expected to kill 10 million people a year by 2050 is that of antibiotic resistance. Any alternatives? Yes, with a century-old therapy, bacteriophage viruses. Phage therapy treats infections with phages, natural viruses that attack bacteria. That's what we used to do before antibiotics. Phage therapy has been empirically applied for decades to treat bacterial infections, notably by the Pasteur Institute in France. The advent of antibiotics during the Second World War led to a drastic reduction in phage therapy. But today, due to the health crisis caused by the emergence and development of antibiotic resistance, the treatment of microbial infections with bacteriophage viruses is back on the agenda, notably through the François Sommer Man Nature 2018 Prize which has just been awarded to the Bacteriophage Network France.

 

Sf nothing moves, the world is heading into a "post-antibiotic era, in which common infections may start killing again," the World Health Organization (WHO) regularly repeats. Antimicrobial resistance already kills 50,000 patients each year in the United States and Europe, and could cause 10 million deaths per year worldwide by 2050, more than cancer, experts commissioned by the British government have predicted. Antibiotic resistance is therefore a growing, and now alarming, threat to global health.

Therapeutic deadlocks are multiplying even though an alternative to antibiotics exists: phagotherapy. Discovered in 1915 by Frederick Twort, phages, these bacterial parasites, were rapidly used as early as 1919 to treat infectious diseases. The use of bacteriophages through phagotherapy is coming back to the forefront as one of the most proven, promising and sustainable avenues for the future.

 

Anyone, at any age and in any country, can now be exposed to the risk of ineffective traditional treatment for even a common bacterial infection. This phenomenon is accelerating, both in humans and animals, simply because antibiotic resistance is a natural phenomenon but also because of the misuse of drugs.

The risk is also increasing as the number of infections increases and the increasing and recurrent difficulty in treating them, leading to longer hospital stays, higher medical expenses and higher mortality. Developing the use of alternative therapies is therefore now recognized as a major global health emergency.

 

The use (and return) of bacteriophages through phage therapy is undoubtedly one of the most proven, promising and long-lasting avenues. In the light of the knowledge accumulated over the last century and in the light of a rigorous medical and scientific approach, but also through the increasingly frequent media coverage of the spectacular results obtained, the re-evaluation of phagotherapy is now on the agenda.

 

The study of bacteriophages and their interactions with bacteria began a century ago with the recognition of their bactericidal action, guiding the Franco-Canadian biologist Félix d'Hérelle to an application in human medicine long before the discovery of antibiotics. But it was above all when they were chosen as objects of study to understand the fundamental mechanisms of cellular life that bacteriophages led to major discoveries, the actors of which were, and still are, rewarded by several Nobel prizes. (1).

From the molecular mechanisms of replication of these viruses (macromolecular assembly, regulation of viral gene expression) to the bacterial defences put in place to counteract them (restriction-modification systems and Crispr-Cas9 ), the study of bacteriophages, using multidisciplinary approaches, has led to real breakthroughs in our knowledge of living organisms.

 

Bacteriophages are also a fascinating biological model of ecology and evolution. In particular, this model allows a better understanding of the emergence and evolution of pathogens.

 

Since their discovery, it was their therapeutic potential that brought bacteriophages to the forefront in treating bacterial infections. Then, as knowledge progressed, their role in the fermentation processes of the food industry (dairy and wine industries) was better understood in order to reduce losses and better control the processes. Today, their use in medicine is again being considered to fight against pathogenic bacteria that have become increasingly resistant to antibiotics and for which sustainable solutions are struggling to emerge. This application makes it possible to envisage the limitation of chemical antimicrobials and thus the pollution of soil and groundwater and will in fact promote the protection of biodiversity.

 

Measures taken to protect humans from microbes have overshadowed the complex ecosystem relationships between organisms and environments in the field of public health. Since bacteriophages are key regulators of the natural microbial communities with which humans must interact at all times, they force us to rethink our relationships with these viruses, first and foremost because of the negative connotations attached to the term. The use of bacteriophages in medicine also engages other representations of care and organisms, in which health no longer appears so much as the exclusion and annihilation of microorganisms, but rather as the coexistence between several species, human and microbial, in a dynamic equilibrium.

 

The Bacteriophage Network France aims to promote, coordinate and integrate studies on bacteriophages across different scientific disciplines, while encouraging the establishment of collaborations and synergies between the teams concerned.

The network initiated by Laurent Debarbieux (Institut Pasteur, Paris) is supported since 2016 by the CNRS and since 2017 by INRA. The INSB and INEE Institutes of the CNRS have joined forces to form a Priority Thematic Network.

In France, around thirty teams are using bacteriophages as a subject of study or as tools to develop applications.

The network allows this community of scientists to share their respective expertise, often related to distinct and specific themes. The approaches developed by these researchers are often complementary and their meeting within the network multiplies the opportunities to create new synergies. The animation of the network has enabled the federation of a community that has become a major player in the French scientific landscape and beyond. (2).

 

Why this science award? The François Sommer Foundation decided in 2012 to create a new scientific prize in France, of international dimension, dedicated to multidisciplinary research work presenting innovative and promising perspectives on the relationship between man and nature. In this way, the Foundation wishes to work for the protection of biodiversity and the respectful use of its resources with a view to sustainable development. A better knowledge and understanding of this biodiversity are essential to any policy or measure for the conservation and management of natural resources and must be a prerequisite for their rational and sustainable use.

 

Conserving biodiversity requires knowledge in several disciplines to respond to the social, economic, cultural, political, ecological and biological issues that this challenge engenders.

Thus, the Foundation considers that only a multidisciplinary scientific approach can provide the expertise and data necessary for a good understanding of biodiversity and its interrelationships with human activities, conditions for harmonious development between man and nature.

The Foundation therefore wished to create a prize to recognize scientific work useful to its action. An ambitious and renowned Prize aimed at honouring exceptional research work making major contributions to today's ecological challenges.

The Prize is open to research that sheds new light on the understanding of the living conditions of living organisms and ecosystems. By investing in unexplored fields, this work provides a different perspective on man's ability to maintain the conditions of harmonious, respectful and profitable interdependence with nature.

Furthermore, like ecosystems whose proper functioning is based on a complex set of interactions between various organisms, and convinced of the major value of decompartmentalized approaches, the Prize seeks to reward scientific work combining the contributions of various scientific disciplines.

Moreover, the interest of a collegial approach is not limited to the scientific field alone. On a daily basis, faced with the challenges of territories and biodiversity, the Foundation, in its action in the field, works in close collaboration and consultation with all the stakeholders in the search for the common interest.

The Prize, which is awarded every two years by a jury of eminent personalities (3)is intended to honour and reveal to the public the career path and/or innovative work of a renowned scientific personality or research centre that is committed to a multidisciplinary approach and offers major advances that combine environmental protection and human development.

 

(1) Major discoveries and Nobel Prizes related to the study of bacteriophages :

1917 Publication of Félix d'Herelle "On an invisible Microbe antagonist of Shiga bacilli".

1952 Discoveries of DNA modification restriction enzymes

1958 Nobel Prize in Physiology or Medicine awarded to Joshua Lederberg for his discoveries on genetic recombination and the organization of the genetic material of bacteria.

1965 Nobel Prize in Physiology or Medicine awarded to François Jacob, André Lwoff and Jacques Monod for their discoveries concerning the genetic control of enzymatic and viral synthesis.

1969 Nobel Prize in Physiology or Medicine awarded to Max Delbrück, Alfred Hershey and Salvador E. Luria for their discoveries concerning the replication mechanism and structure of viruses.

2007 Publication on the role of CRISPR sequences in immunity against bacteriophages

2015 Creation of the Bacteriophage Network France

2018 Nobel Prize in Chemistry awarded to George Smith and Gregory Winter for their work on the expression of peptides and antibodies by bacteriophages.

 

(2) The bureau of the Bacteriophage Network France is composed of recognized scientific and medical personalities: Mireille Ansaldi, Director of Research at the CNRS, Marseille; Pascale Boulanger, Director of Research at the CNRS, Gif sur Yvette; Charlotte Brives, Research Officer at the CNRS, Bordeaux; Laurent Debarbieux, Director of Research at the Pasteur Institute, Paris; Alain Dublanchet, honorary hospital biologist, Vincennes; Rémy Froissart, Research Officer at the CNRS, Montpellier; Sylvain Gandon, Director of Research at the CNRS, Montpellier; Claire Le Hénaff, Professor of Microbiology, Bordeaux Polytechnic Institute (ENSCBP); Marie-Agnès Petit, Director of Research at INRA, Jouy en Josas; Eduardo Rocha, Director of Research at the CNRS, Pasteur Institute, Paris; Clara Torres-Barceló, Research Fellow at INRA, Avignon.

Learn more about the Bacteriophage Network France : www.phages.fr

 

(3) Yves CoppensProfessor (E) at the National Museum of Natural History, (Biological Anthropology), Professor (E) at the Collège de France (Paleoanthropology and Prehistory), member of the Institut de France (Academy of Sciences), member of the National Academy of Medicine.

Pierre Corvol, Professor (E) at the Collège de France (Experimental Medicine), member of the Institut de France (Academy of Sciences), the National Academy of Medicine and the American Academy of Art and Sciences.

Renaud Denoix de Saint MarcVice-President (H) of the Council of State, member of the Institut de France (Académie des Sciences morales et politiques).

Christian DumasProfessor at the Ecole Normale Supérieure (ENS) in Lyon (Reproduction and Development of Plants), member of the Institut de France (Academy of Sciences).

André Laurent Parodi, Professor of pathological anatomy and Director (H) of the National Veterinary School of Alfort, President (H) of the National Academy of Medicine, President (H) of the Veterinary Academy of France.

Yves Pouliquenprofessor of ophthalmology and head of the ophthalmology department at the Hôtel-Dieu de Paris (H), member of the French Academy, member of the National Academy of Medicine.

Claudine Tiercelin, professor at the Collège de France (Metaphysics and Philosophy of Knowledge), member of the Higher Council for Research and Technology, member of the Institut de France (Academy of Moral and Political Sciences).

Cedric Villani, Director of the Institut Henri- Poincaré, Fields Medal in 2010, member of the Institut de France (Academy of Sciences).

The François Sommer Scientific Prize is led by Yves Le Floc'h Soye, full member of the Veterinary Academy of France.