Elaborating on comments made by Levin and Lenski (20
), Abedon (1
) suggested that rapid bacteria acquisition and killing by lytic phages should be favored by natural selection, particularly when bacteria are common but not when bacteria are scarce. By reducing the period of progeny maturation, a phage will release, upon lysis, a smaller number of phage progeny (smaller burst size). The rapidity of phage exponential growth is dependent on more than just the phage burst size, however, and of particular additional relevance is the delay between lysis and progeny acquisition of new host cells (a function of host cell density and the phage adsorption constant) and the delay between adsorption and the maturation of the first phage progeny within a cell (the eclipse period). When these two intervals are short, then phages with shorter periods of progeny maturation may display greater rates of exponential growth than do otherwise identical phages displaying larger burst sizes but longer periods of progeny maturation.
For a given host density (and host quality) there should exist an optimal latent period that represents a balance between the constraints on phage exponential growth that come from too-small burst sizes and the constraints on phage exponential growth that come from too-long latent periods. In homogeneous environments of large volume of those phages that have minimized their likelihood of inactivation, time until adsorption, eclipse period, and the time it takes to lyse their host cell (once lysis has been initiated), and have maximized their rate of intracellular progeny maturation, only those lytic phages that additionally display an optimal latent period will also display maximal rates of host cell acquisition, bacteria lysis, and phage population growth. Here we have refined models of phage growth to make quantitative predictions of phage latent-period optima as a function of both host quantity and host quality. These efforts strongly parallel earlier efforts by Wang et al. (29
). However, by employing a more complex, more realistic, and more standard (21
) method of modeling phage adsorption, we predict that latent-period optima can be substantially shorter at lower host densities (Fig. and ) than those suggested by Wang et al. And, as suggested by Kokjohn et al. (18
), it is likely that there exists no fundamental reason for why phage replication could not occur at even very low host or nutrient densities.
The study of phages in the laboratory typically involves the productive infection of hosts grown on relatively rich media. Latent periods may be determined experimentally and may be modified through either changes in phage genes or via the manipulation of host physiology. Individuals with an interest in the control of lysis timing ultimately should ask why a given phage isolate employs a certain latent period under a given set of conditions rather than one that is longer or one that is shorter. A reasonable assumption is that a phage's latent-period genotype underlies an in situ latent-period phenotype that has evolved to maximize a phage's Darwinian fitness. Interpreting measurements of latent period in terms of phage in situ evolution, however, is complicated by differences in host quality between the laboratory and a phage's growth environment outside of the laboratory. We find here, though, that the physiological component of differences in the latent-period optima with one host quality versus another may be sufficiently large (dotted lines versus diamonds and circles in Fig. ) that, in fact, laboratory determinations of latent period and latent-period optimization may be more applicable to phage in situ growth than we could previously have appreciated. We predict, therefore, that it may be difficult to confirm the predictions of our models in terms of the evolution of phage latent period in response to changes in host quality.
By contrast, though we expect smaller differences with changes in host density than those predicted by Wang et al. (29
), we still expect host density to be a reasonably strong determinant of phage latent-period optimization (Fig. ), and we find that experimental evidence is consistent with a conclusion that lower host densities select for longer phage latent periods, while higher host densities select for shorter phage latent periods. Hershey (17
), for example, competed T-even phages possessing short latent periods (rapid lysis mutants) with wild-type T-even phages displaying conditionally longer latent periods (lysis inhibition). Wild-type phages out-competed rapid lysis mutants during growth in broth culture. Presumably this occurs, at least in part, because the longer latent periods displayed upon lysis inhibition are an adaptation by T-even phages to environments in which uninfected host densities are declining (2
As with lysis inhibition, we can also consider phage reduction to lysogeny as an example of an inducible extension of the phage latent period, though one in which the eclipse period is extended rather than the period of progeny maturation. Just as with lysis inhibition, reduction to lysogeny is thought to occur with greater likelihood when phage multiplicities are greater than 1 (14
). This is a circumstance during which uninfected host densities should be in decline.
We additionally have initiated a more direct approach to testing the predictions made by our models. In these experiments we compete various phages that differ in terms of latent period and burst size. Because of a slightly faster rate of exponential growth in the presence of relatively high densities of host cells (~107 to ~108 cells/ml), we find relatively strong selection, versus that of the wild-type parent, for a phage mutant that displays a latent period that is ~25% shorter than that of the wild type. This mutant's growth advantage occurs despite its displaying a burst size that is only about one third that of the wild type (S. T. Abedon, unpublished data).
The impact of lytic phage latent-period optimization should be to make bacteria more rapidly acquired by phages and thereby less available to nonphage consumers of bacteria. Optimization as we are defining it, however, demands a constant host density and a constant host quality. We might suppose that variation in host density or quality over time or space would serve to reduce the optimality of phage growth and therefore reduce the relative rapidity with which a given phage population can exploit a given host population. Consequently, we envisage a constant selection for increasingly optimized phage latent periods, but ultimately we expect ecosystems to vary sufficiently in both space and time that the end point of successful latent-period optimization is effectively never attained.