Bacteriophages

The growing number of drug-resistant bacteria is an emerging global health crisis that requires alternative approaches. Current research indicates that bacteriophages (phages), viruses infecting bacteria, can represent a viable alternative, or be part of conventional antimicrobial therapy in combination with antibiotics or other molecules/therapies, to treat bacterial infections.

Bacteriophages specifically kill bacteria, showing antimicrobial activity against a wide range of resistant bacterial species, without infecting other organisms. They are ubiquitous in all ecosystems (terrestrial and aquatic), including plant, animal and human microbiomes, and are able to be used as a one health strategy to fight antibiotic resistance.

The practice of phage therapy started in 1919, in Eastern Europe, and continues today in the clinical setting, but in Western Europe and the USA, phage therapy continues to lack any market approval. However, phage therapy has been increasingly used as an experimental therapy for the compassionate treatment of patients experiencing antibiotic failure. Moreover, in recent years, promising clinical studies of phage therapy were/are conducted to treat human infections caused by antibiotic-resistant bacteria. Nonetheless, soon after the appearance of the first successful results of phage therapy in human medicine, the knowledge was quickly translated to other areas such as veterinary medicine, the food industry, agriculture and aquaculture, where this approach has been well received and some applications have already been approved.

While the efficacy of phage therapy has proven to be an efficient alternative/coadjuvant to conventional antibiotics, there is still need for new developments to translate the approach to routine treatment. In the clinical setting, besides fighting infections caused by drug-resistant bacteria, phages can be useful even when bacterial strains are still sensitive to antibiotics, such as in the treatment of infections caused by intracellular bacteria, infections caused by bacteria that form biofilms, chronic bacterial infections, infections in areas inaccessible to antibiotics, such as wounds and diabetic foot ulcers, which affect patients with poor circulation, and even in the treatment of systemic bacterial infections.

In non-clinical settings, it is imperative to study the impact of phage use on the environment and also the effect of abiotic factors on phage viability, such as temperature, pH, salinity and UV radiation, particularly if phage treatment will be used outside where these parameters vary throughout the year. The structural and functional stabilization/preservation of phage particles in supports may be an important strategy to overcome the negative effect of these abiotic factors.

For both clinical and non-clinical applications, the need to prevent the development of phage-resistant mutants, which can be hampered by the use of phage cocktails, phage combined approaches, engineered phages and application of novel phages, is also a relevant aspect. Consequently, phage therapy sucess requires access to large phage libraries that must be maintained and constantly supplied with novel phages targeting the phage-resistant mutants. Additionally, in general, more ex vivo and in vivo studies, as well as the establishment of phage therapy regulatory pathways, are also imperative to translate the technology to practice.