Kinetics of Phage-Mediated Biocontrol of Bacteria

Bacteriophages (phages) are the viruses of bacteria. One subset of phages, those that can be described as obligately lytic, can effect an active phage therapy because their population growth occurs at the expense of bacterial survival. That is, phages can be employed to reduce bacterial loads-such as in animals preslaughter, in foods postharvest, or in humans postinfection- and in the process can actually increase what in pharmacological terms would be their antibacterial dose. This self-amplification may provide advantages if either antibacterial dosing or penetration to target bacteria is otherwise constrained. One situation in which these kinetic aspects of drug delivery may be constrained is in preslaughter treatment of food animals toward control of zoonotic pathogens (e.g., Escherichia coli O157:H7 in cattle). In such treatment, the self-amplifying nature of phages may be harnessed, though potentially under time constraints. In this discursive I cover three areas. The first is semantic, where I contrast the terms phage therapy and phage-mediated biocontrol of bacteria, both of which are employed to describe similar but perhaps not identical procedures. Second, I consider the importance of time in therapy or biocontrol procedures while contrasting passive versus active therapies. Third, I discuss conceptually how to go about modifying phage characteristics to increase rates of phage population growth and do so explicitly by casting phage infection in terms of Michaelis-Menten saturation kinetics. I conclude suggesting that phage therapy ultimately may be rationally guided by theoretical considerations of the impact of phage properties on rates of phage population growth.