Editorial: Phage therapy: Past, present and future

As an ancient proverb states, “The enemy of my enemy is my friend.” The so-called strictly lytic or virulent bacteriophages (phages)—especially the viruses of pathogenic bacteria—can certainly be considered enemies of “bad” bacteria and thereby our friends. The phage potential as antibacterial agents was recognized almost immediately upon the first generally accepted descriptions of these viruses as transmissible bacteriolytic entities (Abedon et al., 2011). As this was prior to Fleming's (1929) discovery of naturally occurring antibiotics, rather than being named as variations on that theme, the Greek concept of “phage” was chosen instead (d'Hérelle, 1917). “Phage” seemingly is a description of the macroscopic impact these viruses have on bacteria, which to the eye appear to be “eaters” or “devourers” of bacterial cultures (Summers, 1991), in broth or solid media.

The therapeutic, antibacterial application of phages came to be known as phage therapy, especially in clinical or veterinary contexts. More broadly, phages have also been used as biological control agents, reducing bacterial loads in foods, e.g., such as of Listeria monocytogenes in food processing (Bai et al., 2016), of zoonotic pathogens in food animals (Atterbury, 2009), or, in the treatment of crops against plant pathogenic bacteria as reviewed by Buttimer et al. Furthermore, modified phages can be used as DNA, protein, or drug delivery vehicles (Clark et al., 2012), and non-bacterial viruses can be used as biological control agents as well (e.g., Hyman et al., 2013; Kondo et al., 2013; Gilbert et al., 2015). Phage study, whether ultimately for therapy or biocontrol, spans from purely clinical observation to molecular analysis to considerations of immunology as well as ecology, the latter as phages represent essentially “living” drugs. In addition is the development of enzybiotics, which are therapeutic enzymes and most prominently include phage endolysins. The latter are proteins which phages employ to lyse the bacteria they are infecting, thereby releasing intracellularly produced phage progeny (Fischetti, 2008).