Many publications list advantages and disadvantages associated with phage therapy, which is the use of bacterial viruses to combat populations of nuisance or pathogenic bacteria. The goal of this c...

In this commentary I consider use of the term “lysis from without” (LO) along with the phenomenon’s biological relevance. LO originally described an early bacterial lysis induced by high-multiplici...

Bacteriophages (phages) modify microbial communities by lysing hosts, transferring genetic material, and effecting lysogenic conversion. To understand how natural communities are affected it is important to develop predictive models. Here we consider how variation between models—in eclipse period, latent period, adsorption constant, burst size, the handling of differences in host quantity and host quality, and in modeling strategy—can affect predictions. First we compare two published models of phage growth, which differ primarily in terms of how they model the kinetics of phage adsorption; one is a computer simulation and the other is an explicit calculation. At higher host quantities (∼10⁸cells/ml), both models closely predict experimentally determined phage population growth rates. At lower host quantities (10⁷cells/ml), the computer simulation continues to closely predict phage growth rates, but the explicit model does not. Next we concentrate on predictions of latent-period optima. A latent-period optimum is the latent period that maximizes the population growth of a specific phage growing in the presence of a specific quantity and quality of host cells. Both models predict similar latent-period optima at higher host densities (e.g., 17 min at 10⁸cells/ml). At lower host densities, however, the computer simulation predicts latent-period optima that are much shorter than those suggested by explicit calculations (e.g., 90 versus 1,250 min at 10⁵cells/ml). Finally, we consider the impact of host quality on phage latent-period evolution. By taking care to differentiate latent-period phenotypic plasticity from latent-period evolution, we argue that the impact of host quality on phage latent-period evolution may be relatively small.

Phage therapy—application of bacteria-specific viruses to reduce densities of pathogenic or nuisance bacteria— is a two-step process involving phage penetration to target bacteria followed by bacteria killing. Any analysis of these steps is inherently ecological as they represent phage-environment interactions, i.e., between phages and bacteria as well as between phages and body tissues. In considering phages more generically, as selectively toxic antibacterial agents employed to treat bacterial infections, the term “ecology” may be fairly cleanly replaced with the term “pharmacology”. Pharmacology, in turn, may be distinguished into two major components: pharmacokinetics and pharmacodynamics. Pharmacokinetics is explicitly a description of the bodys impact on a drug (e.g., movement through and between body compartments) whereas pharmacodynamics is a description of a drugs impact on the body. “Body” includes both body tissues and microbial flora, so an important component of antibacterial pharmacodynamics is inhibition of the growth of target bacteria. Our guiding premise is that phage therapy may be rationally improved through a better understanding of phage pharmacokinetics and pharmacodynamics. Our primary conclusions are (i) that the principle advantages of phages, over antibiotics, are the formers relative safety and ease of discovery; (ii) that phage therapy efficacy is highly dependent on attaining relatively high phage “killing titers”; (iii) that attainment of sufficient titers solely via in situ phage replication should, in some or many circumstances, not be counted upon; and (iv) that phage replication nonetheless may provide a “margin of safety” toward attaining phage therapy efficacy.

Bacteriophages, or phages, are viruses of the members of domain Bacteria. These viruses play numerous roles in shaping the diversity of microbial communities, with impact differing depending on what infection strategies specific phages employ. From an applied perspective especially are communities containing undesired or pathogenic bacteria that can be modified through phage-mediated bacterial biocontrol, that is, through phage therapy. Here we seek to categorize phages in terms of their infection strategies as well as review or suggest more descriptive, accurate, or distinguishing terminology. Categories can be differentiated in terms of (1) whether or not virion release occurs (productive infections vs. lysogeny, pseudolysogeny, and/or the phage carrier state), (2) the means of virion release (lytic vs. chronic release), and (3) the degree to which phages are genetically equipped to display lysogenic cycles (temperate vs. non-temperate phages). We address in particular the use or over-use of what can be a somewhat equivocal phrase, “Lytic or lysogenic”, especially when employed as a means of distinguishing among phages types. We suggest that the implied dichotomy is inconsistent with both modern as well as historical understanding of phage biology. We consider, therefore, less ambiguous terminology for distinguishing between “Lytic” versus “Lysogenic” phage types.

Phage therapy is the use of bacterial viruses as antibacterial agents. A primary consideration for commercial development of phages for phage therapy is the number of different bacterial strains that are successfully targeted, as this defines the breadth of a phage cocktail’s spectrum of activity. Alternatively, phage cocktails may be used to reduce the potential for bacteria to evolve phage resistance. This, as we consider here, is in part a function of a cocktail’s ‘depth’ of activity. Improved cocktail depth is achieved through inclusion of at least two phages able to infect a single bacterial strain, especially two phages against which bacterial mutation to cross resistance is relatively rare. Here, we consider the breadth of activity of phage cocktails while taking both depth of activity and bacterial mutation to cross resistance into account. This is done by building on familiar algorithms normally used for determination solely of phage cocktail breadth of activity. We show in particular how phage cocktails for phage therapy may be rationally designed toward enhancing the number of bacteria impacted while also reducing the potential for a subset of those bacteria to evolve phage resistance, all as based on previously determined phage properties.