FIG 2.

Approaches to phage therapy delivery. A schematic representation of a bacterial cell consisting of capsule, outer membrane, cell wall, inner membrane, and cytoplasm is shown. (A) Phage lytic life cycle as the basis for conventional monophage therapy, from adsorption to lysis of the host cell, and polyphage therapy, or use of phage cocktails targeting different receptors on the same host cell, limiting the occurrence of resistance and expanding the therapeutic spectrum. (B) Use of phage-derived enzymes such as depolymerases (to target capsules and biofilm structures) and cell wall-degrading endolysins. Holins, spanins, and virion-associated peptidoglycan hydrolases (VAPGH) are represented as components of the lytic life cycle, without current therapeutic applications. (C) Mechanisms for synergy between phages, antibiotics, and the immune response include phage-mediated capsule or biofilm degradation, which enables the action of antibiotics, antibodies, the complement system, and phagocytes, and the exploitation of the evolutionary trade-offs of phage resistance, such as antibiotic resensitization and impaired bacterial growth. (D) Bioengineering of phages for therapeutic purposes includes the attachment of antibiotics or photosensitizing agents to phage capsids for targeted release into bacterial cells, delivery of genes to reverse/cancel antibiotic resistance and virulence determinants, and use of chimeric phages. Labels in italic represent bacterial structures.