LThe FAGOMA Thematic Network aims to jointly face a series of challenges, all of them aligned with the Challenges of Society that are planned in the Spanish Strategy for Science and Technology and Innovation and that we could summarize in the following:

Challenge 1.- Improvement of food quality and safety.

At present, concern for the quality and safety of food continues to be a priority in our society, which also faces the challenge of making it compatible with sustainable production adapted to the growing demand for food. As a whole, these research groups address the different aspects of bacteriophages and their relationship with food, from those that cause a problem in the food industry, to those that can be used as a solution, and for this, they are studying from basic biology to aspects related to its application in the food industry.

Challenge 2.- Obtaining new antimicrobials.

The constant increase in infections caused by multiresistant bacteria to antibiotics has generated an international alarm that has been showed by the World Health Organization (WHO) through its action plan against antibiotic resistance. One of the objectives of this plan is the development of new antimicrobials that are capable of eliminating resistant bacteria, since we are hopelessly doomed to the post-antibiotic era. In addition, control of the spread of resistance must be carried out through the concept of “One Health” that promotes a joint strategy that encompasses not only the human population, but also a control in the use of antibiotics and biocidal substances in farms, industries, etc., which are subsequently discharged into the environment. The antimicrobial capacity of phages makes it possible to reduce the bacterial load in farm animals, thus reducing the probability of transmission of zoonotic bacteria to the food chain and avoiding the use of antibiotics for disease control in the primary sector. Similarly, bacteriophages can also be used in the control of phytopathogenic bacteria. Endolysins (enzybiotics) have a high antimicrobial activity against pathogens that has been demonstrated in animal models of infection. A clear objective is to develop phage products applicable to the treatment of bacterial infections resistant to antibiotics in humans.

Challenge 3.- Development of application tools in biomedicine.

The future of health care involves the development of personalized medicine, in which the analysis of the genomic and clinical data of the patient will make it possible to prevent and treat diseases, anticipating what the response to treatment will be, which will be personalized for each patient. In addition, advances in the editing of the human genome will make it possible to repair defects and prevent or cure certain diseases in an individualized way. All these advances require highly sophisticated tools, ranging from those that allow genetic manipulation, to those necessary for the development of very precise diagnostic techniques. The study of DNA replication and recombination processes using bacteriophages as a model has led to important applications in biotechnology and medicine, such as the development of diagnostic kits for diseases as important as cancer. On the other hand, bacteriophage experimental evolution systems allow us to understand the adaptation processes and the factors that govern genetic diversity, and which are also used for the selection of viruses as therapeutic agents. The research groups involved in this challenge are experts in bacteriophage molecular biology seeking applications for the diagnosis and treatment of diseases and also in multiple fields of biotechnology.

Reto 4.- Frenar lChallenge 4.- Stop the spread of antibiotic resistance mediated by bacteriophages.

Horizontal gene transfer is the main mechanism of evolution in prokaryotes; this transfer is mediated by mobile genetic elements (plasmids, transposons, pathogenicity islands and bacteriophages). In the case of pathogenic bacteria, to know the dispersal mechanisms, in certain environments, of antibiotic resistance genes, or virulence genes in general, is of special interest. Phages act as vehicles for transmission from the genomes of the bacteria themselves (generalized and specialized transduction) or as carriers of certain genes in their genomes (morons) that can later be stabilized in the bacterial genome by lysogeny. In other cases, mobilization is carried out by pathogenicity islands that are activated after phage infection. These islands are packaged in modified phage capsids to suit their new role. Phages can carry toxins and antibiotic resistance genes, so studies on the distribution of these phages in environmental samples, animals, food and wastewater, etc. are of great interest for the design of control strategies.

Challenge 5.- Elucidate the role of bacteriophages in microbiomes.

Advances in culture-independent microorganism identification techniques have opened the door to a deeper understanding of the viruses and bacteria that make up natural microbial ecosystems. An example is marine ecosystems, essential for the functioning of the planet, since they participate in the transformation of chemical elements such as carbon, nitrogen, phosphorus, oxygen, etc., and of enormous importance in trophic chains or in the climate. Together, the different research groups are experts in the management of cutting-edge genomics and proteomics techniques, and their studies are clearly related to the knowledge of the evolution of bacteriophages and their role in natural environments. It should be noted that ocean-related studies are vitally important for Blue Growth, an EU strategy to support sustainable growth in the marine and maritime sectors. Ecosystems as different as the Arctic or the Mediterranean are being studied, where the lytic and lysogenic cycles of phages have a great impact on bacterial populations. Furthermore, the application of metagenomics and metatranscriptomics techniques to the study of microbial communities has made it possible to propose models of the evolution of prokaryotic populations and of the bacteriophages that infect them. Finally, culture-independent Individual Virus Genomics technology is useful to deepen our understanding of the human microbiome and virome, which is highly relevant for human health.

Challenge 6.- Design of nanomachines.

The study of the three-dimensional structure of proteins and much larger protein complexes, such as phage particles, requires very complex techniques such as crystallography, electron cryomicroscopy, cryotomography, etc. The results obtained from these studies are essential to understand the processes of morphogenesis of bacteriophages and also have application in various fields of study. For example, the structure of some phage proteins has made it possible to specifically modify some regions to adapt their function to a specific requirement. Thus, in the improvement of phage therapy, the knowledge about the structure of the fibers proteins of the bacteriophages and the bacterial receptors allows to modify and expand the host range, in order to increase its effectiveness in therapeutic applications.