🔬 Phage Takes

Bacteriophage Ecology Group News, or BEG News, was published mostly quarterly as an online newsletter for a total of 26 issues, starting July 1, 1999 and continuing through December 31, 2007. As follows is a reprint of the editorial from the newsletter. Also included in issues were lists of new members to the Bacteriophage Ecology Group, an introduction to new website features, a list of upcoming meetings, phage images found on the web (remember, this was 1999, so effectively pre-Google), etc., but most of all, a listing of new phage ecology-related publications. The newsletter was modelled after T4 News, which was a printed newsletter distributed earlier in the 1990s. The newsletter's successors are the ongoing Phage.org website, phage-therapy.org, and the Bacteriophage Ecology Group Facebook page.

The Bacteriophage Ecology Group (BEG) is concerned, of course, with the ecology of bacteriophages. When modeling bacteriophage growth, especially in liquid culture, the dynamics of host acquisition by bacteriophages should essentially resemble those of any organism that acquires its "prey" through random diffusion. Of organisms that obtain their resources directly from other living organisms, we may, of course, further subdivide into (i) those that acquire no more than one "prey" per lifetime (the parasites) and (ii) those that acquire more than one "prey" per lifetime (the predators). An individual bacteriophage clearly cannot acquire more than one "prey" (or host) in a lifetime so clearly, by these definitions, is more parasite-like than predator-like.

Among parasites we may further subdivide into (i) those parasites that infect multicellular organisms and (ii) those parasites that infect unicellular organisms. From the standpoint of a parasite, the former, but not the latter, is supplied with additional "prey" by the infected host. This is most easily visualized when considering obligately lytic intracellular parasites in which host cells represent discrete "prey." Thus, acquisition of a single host cell can lead to the generation of parasite progeny which can then go on to acquire new "prey," all without any parasite ever leaving the original host. This is not the case for the parasites of unicellular hosts (or unicellular organism parasites, i.e., UOPs). The progeny of UOPs must leave their host (e.g., an individual bacterium) to acquire new "prey." It has been my policy to define UOP rather broadly to include such parasites as Bdellovibrio as well as the viruses of yeasts and those of protozoa.

Nevertheless, ambiguity rears its ugly head in defining multicellularity. An important component of the first night of the 1999 Gordon Conference on Microbial Population Biology (held July 18-23) was the argument that bacteria often exist effectively as multicellular organisms. That is, individual cells interact in ways such that the whole of a bacterial population is greater than (or, at least, different from) the sum of its parts. If bacteria can be multicellular, then are bacteriophages truly UOPs? Is anything?

I won't attempt to answer that question but instead will address the implications of bacterial multicellularity on bacteriophage replication, based on a contrast between the environments represented by multicellularity versus those represented by unicellularity. I will then question whether, from the standpoint of bacteriophage growth, eukaryotic cells growing in tissue culture are any more multicellular than, for example, bacteria growing in a biofilm or bacteria growing within an agar lawn or colony.

With regard to the population-wide growth of obligately intracellular parasites, two considerations may occur during the jump from unicellularity to multicellularity. First, the susceptibility of individual host cells to parasite infection may decline. Second, the dynamics of host-cell acquisition may change. Considering the former, we may envisage barriers to parasite diffusion, changes in host cell-surface markers, or even mechanisms of parasite inactivation both prior to and following host-cell infection (e.g., an immune system). Alternatively, with regard to the dynamics of host-cell acquisition, clearly with multicellularity the odds of finding two host cells that are adjacent is no longer a statistically independent product of global host-cell densities. Thus, within a multicellular system the acquisition of a single host cell increases the likelihood or rate with which progeny may find additional host cells. Clearly these two factors would result in (i) a decrease in host-cell susceptibility and (ii) an increase in host-cell clumping.

Together these factors affect parasite replication in opposite directions with the former decreasing and the latter increasing host susceptibility in terms of the spread of progeny parasites to adjacent cells. We may thus envision that if parasitism has significant negative impact, then the benefits of multicellularity to the host must either outweigh the costs of increased parasite susceptibility by multicellular organisms or that along with multicellularity comes at least an opportunity for increased defense against parasites. If the latter is the case then one might even go so far as to argue that multicellularity could have evolved in general as a mechanism of parasite (or predator) evasion. For example, the evolution of metazoa could have been motivated as a mechanism of protection against protozoa-mediated engulfment (i.e., big things are harder to engulf and multicellularity is one route toward bigness). Alternatively, as well as additionally, multicellularity may have evolved as a means toward more-effective predation of, for example, multicellular cyanobacterial mats.

Thus, a multicellular organism represents both a juicier, perhaps more obtainable target for parasitism, but simultaneously a less appetizing morsel to the extent that colonial living leads to mutual protection against parasitism. Since prokaryotes are probably as capable of at least some mutual protection as eukaryotes, then I suppose I must concede that bacteria, from the point of view of a bacteriophage, are not nearly as unicellular as I might otherwise like to think. How, then, might we classify eukaryotic cells living together in a tissue culture flask? Are such cells any less susceptible to a parasite than bacteria living in an agar lawn or within a biofilm? My intuition suggests no. I welcome (and would like to publish) any good arguments either for or against this assertion.

All of this pontification stems from a debate I've been having with myself over whether we should include an article — found in the September 10 issue of Science on vesicular stomatitis virus evolution — into the BEG bibliography: Rosario Miralles, Philip J. Gerrish, Andrés Moya, and Santiago F. Elena, Clonal Interference and the Evolution of RNA Viruses, Science 285(5434):1745-1747 (Clonal Interference). Since the primary experimental technique used in this study involves little more than growing viruses on "baby hampster kidney cells... grown as monolayers under Dulbecco's modified Eagle's minimum essential medium," it strikes me that what we have here is an example of UOP-mediated experimental evolutionary biology. Therefore, along with UOP ecology and evolutionary biology in general, it is my tentative contention that Miralles et al. should be included in the BEG bibliography (along with, for example, papers on the viruses of protozoa). What do you think?