Antibiotics have revolutionized the treatment of infectious diseases. Unfortunately, antimicrobial resistance (AMR) is today a global problem that requires an integral solution. AMR is responsible for an estimated 25,000 deaths per year in the EU and 700,000 worldwide. A report commissioned by the UK government in 2016 predicts that by 2050, AMR infections will kill 10 million people across the world, representing more than the current toll from cancer. One of the most promising alternatives to antibiotics is phage therapy – i.e. the use of viruses (bacteriophages) to specifically infect and kill bacteria. From an ecological perspective, (bacterio)phages are the most abundant and ubiquitous organisms on Earth, and play important roles in microbial physiology, population structure, dynamics and ecosystem functioning. Phages have the advantage to be extremely strain-specific and do not have a major impact on the commensal flora.
The appearance and increase of AMR observed throughout the world cannot be explained only by the modern and growing use of antibiotics, as it implies a complex interaction of microbial communities, antibiotics and AMR genes from different ecosystems. In addition, horizontal gene transfer is the most relevant form of AMR propagation and is mediated by elements capable of transferring genetic information from one bacterium to another. The bacterial modulator properties of phages make them suitable vehicles for the mobilization of genes between microorganisms from different ecosystems.
The general objective of this project is to understand the role of phages in the emergence, abundance and dissemination of AMR genes in human-impacted environments. Ultimately, a major exploitation goal consists of the recovery and characterization of novel phages with potential for the development of alternative antimicrobial therapies.
We have unveiled an unprecedented amount of novel phages through culture-independent (agricultural soil) and culture-dependent (staphylococcal phages from wastewater) approaches, with complex and extended phage-bacterial networks. Our huge data set substantially increases the amount of currently available viral data, and provides insights into the yet largely undescribed environmental viral sequence space. We are further characterizing relevant phages for (i) their ability to mobilize AMR genes and (ii) their properties to be exploited for the development of novel antimicrobial strategies.
