The clinical path to deliver encapsulated phages and lysins

The global emergence of multidrug-resistant pathogens is shaping the current dogma regarding the use of antibiotherapy. Many bacteria have evolved to become resistant to conventional antibiotherapy, representing a health and economic burden for those afflicted. The search for alternative and complementary therapeutic approaches has intensified and revived phage therapy. In recent decades, the exogenous use of lysins, encoded in phage genomes, has shown encouraging effectiveness. These two antimicrobial agents reduce bacterial populations; however, many barriers challenge their prompt delivery at the infection site. Encapsulation in delivery vehicles provides targeted therapy with a controlled compound delivery, surpassing chemical, physical and immunological barriers that can inactivate and eliminate them. This review explores phages and lysins' current use to resolve bacterial infections in the respiratory, digestive, and integumentary systems. We also highlight the different challenges they face in each of the three systems and discuss the advances towards a more expansive use of delivery vehicles.MDS and AMP acknowledge the Portuguese Foundation for Science and Technology (FCT) grants SFRH/BD/128825/2017 and SFRH/BD/138138/2018, respectively. National funding by FCT, through the individual scientific employment program-contract with SS (2020.03171.CEECIND). This study was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2020 unit and BioTecNorte operation (NORTE-01-0145-FEDER-000004) funded by the European Regional Development Fund under the scope of Norte2020 - Programa Operacional Regional do Norte. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 713640.