Phascinating Phages

Abstract

Treatment of infections caused by bacteria has become more complex due to the increasing number of bacterial strains that are resistant to conventional antimicrobial therapy. A highly promising alternative appears to be bacteriophage (phage) therapy, in which natural predators of bacteria, bacteriophages, play a role. Although these viruses were first discovered in 1917, the development of phage therapy was impacted by the discovery of antibiotics, which spread more quickly and effectively in medical practice. Despite this, phage therapy has a long history in Eastern Europe; however, Western countries are currently striving to reintroduce phage therapy as a tool in the fight against diseases caused by drug-resistant bacteria. This review describes phage biology, bacterial and phage competition mechanisms, and the benefits and drawbacks of phage therapy. The results of various laboratory experiments, and clinical cases where phage therapy was administered, are described.

Keywords: antibiotic therapy; bacteriophages; drug-resistant bacteria; phage therapy.

Figure 1

Life cycle of bacteriophages. First, the phage adsorbs to the bacterial cell receptor (1). Second, it forms a pore in the membrane and phage NA is injected into the host cell (2). As the virus continues the lytic cycle, viral proteins are produced, phage NA (3a) replicates, and virion assembly (4a) and cell lysis (5a) occur. During the lysogenic cycle, the phage integrates its genome into the host chromosome (3b) and replicates with it (4b). Changing conditions may induce a transition to the lytic cycle.

Figure 2

Mechanisms of bacterial resistance to phage infection. Prevention of phage adsorption to the surface of bacterial cells due to alteration of the surface receptor or production of protective surface polysaccharides (1). Prevention of phage NA injection by modification of inner membrane proteins (2). Reducing the number of free infectious bacteriophage particles by producing membrane vesicles (3). Degradation of phage NA by the restriction modification system (4) or the CRISP-Cas system (5). Prevention of phage NA replication by secondary bacterial metabolites (6). Inhibition of the assembly of phage particles by blocking terminase or scattering envelope proteins (7). Limitation of phage particle production by induction of cell death (8).