PNAS Early Edition has a paper that phage enthusiasts should read. I was alerted to it by this Economist piece. Symbioses are widespread and the focal paper adds animal mucosa to the list of ecosystems where they play a critical role. The paper convinces me that lytic phage are actively recruited by metazoan cells to reduce the colonization of mucous layers by pathogenic bacteria. All the relevant steps in reasoning are there: the relative enrichment of bacteriophage in mucous layers (relative to the ~10:1 ratio found in adjacent microenvironments or in the marine environment), the mechanism of attachment (immunoglobulin-like protein domains expressed on the capsid of phage T4 – their model – attach to mucin glycoproteins) and the lysis-mediated reduction in bacterial numbers. The authors used a number of clever methods in their assays including a modified phage overlay assay to quantify reductions in colonization in vitro, and an amber mutant phage to confirm that lysis conferred the protective effect.
The paper ends by considering the role that lysogenic phage may play in protecting commensal bacteria. This reminds me of an argument made here and elsewhere that resistance to potential parasites and tolerance of them (by for example repairing the damage they do) have divergent ecological and evolutionary consequences that can feedback on the expected prevalence of these mechanisms. Loosely speaking, the argument is that resistance to invaders (by definition) imposes costs on them. Selection occurs for immune evasion (virulence) in the invader population, in turn selecting for a variant host resistance allele in an arms race. Resistance alleles are therefore not subject to sustained positive selection in the host, but instead show transient or frequency-dependent selection dynamics. Tolerance, on the other hand, permits populations of the invader to persist and, in its purest form, imposes no costs on them. Therefore host tolerance alleles experience sustained positive selection and an elevated geometric mean fitness (which seems to be what selection “likes”).
The focal paper plays into this argument in two ways that I can see. First, the presence of an adaptive immune system or an adaptive component of the innate response mediated by phage may bolster the efficacy of what might be termed “meta-resistance” alleles in the host. In this case, meta-resistance alleles are those that modify/form glycoproteins to support phage attachment. Second, and on the side of tolerance, it is possible that lysogenic phage could be recruited to modify the virulence of the pool of invading micro-organisms either indirectly, through ecological interactions, or directly, through modification of bacterial genomes. Of course, the distinction between resistance and tolerance is a false dichotomy, but I find it useful to keep in mind. Since vertical transmission is a relevant factor for the explanatory utility of the Red Queen, it would also be interesting to know whether phage communities themselves are stable over longer periods and between animal generations.
After reading and enjoying Forest Rohwer’s very accessible book on coral reef ecology and noting his authorship in the focal paper, I anticipate a future book of mucosal musings…