Phage Therapy: a potential solution to fight antibiotic resistant infections

The emergence of bacteria resistant to antibiotics has become a global public health threat.

 According to the World Health Organization (WHO), Antimicrobial Resistance (AMR) is associated with more than a million deaths every year. Recent projections associate AMR to 8.2 million deaths annually by 2050 if no solutions to stop AMR progression are found. This alarming prediction, in addition to a limited pipeline for new antibiotics, has motivated a renewed interest in bacteriophages as possible alternatives or adjunct to conventional antibiotics.

Bacteriophages, also known as phages, are viruses that specifically infect bacteria, independently of their antibiotic resistance profile. They are harmless to human, animal, or plant cells. They are considered the most ubiquitous biological entities in the biosphere and are thought to be ten times more numerous than the bacterial population estimates. Phages were discovered over a century ago, and their potential to treat bacterial infection diseases was, at that time, immediately recognized.

Bacteriophages can be classified as virulent or temperate according to their mode of infection. Virulent phages lyse their bacterial host at the end of a replication cycle while temperate phages may integrate their genome into the bacterial genome. It is this ability of virulent phages to solely kill and lyse bacteria that is the basis of their therapeutic application to treat bacterial infections, the so-called Phage Therapy. Although Phage Therapy has been in use for a century in Eastern countries, particularly in Georgia, its use in the USA and Europe is recent and limited to specific patients with difficult-to-treat bacterial infections, after standard antibiotic treatments had failed. This personalized bacteriophage therapy is applied under local regulations. Although an increasing number of successful phage therapies has been reported, a potential broader adoption of phage therapy still requires robust data to ensure safety and efficacy of phage products. To date, there is no phage-based medicinal product for human use approved under EU or USA law. However, efforts from Medicine Regulatory agencies are in progress and discussion on regulatory aspects relating to phage therapy is taking place.

The development of phage therapy for use in human infections requires engagement of academia, industry, governments and regulatory and funding agencies.

The PhaBRIC group at the Research Institute of Medicines, Faculty of Pharmacy (iMed.ULisboa) studies bacteriophage-bacteria interactions, being engaged in the development of phage-based products for therapeutic application, particularly targeting bacterial pathogens that are part of the WHO global list of most problematic antibiotic-resistant bacteria.

 

Professora Doutora Madalena Pimentel