The main goal of this meeting was to get a better appreciation of the role of phages in the Biosphere… For this, were brought together 20 world leaders working on different aspects of the issue.
Stephen Abedon, Mya Breitbart, Harald Brüssow, Sherwood Casjens, Martha Clokie, André M. Comeau (Organiser), Mike Dyall-Smith, Jonathan Filée, Patrick Forterre, Graham F. Hatfull, Christine Jessup, Henry M. Krisch (Organiser), Debbie Lindell, Nicholas H. Mann (Organiser), David Prangishvili, Ruth-Anne Sandaa, Curtis Suttle, K. Eric Wommack.
by André M. Comeau, Henry M. Krisch and Nicholas H. Mann
26-31 March, 2007
Phage Interactions with the Environment
Stephen Abedon focused on how phage evolved to exploit their host’s resources. The parameters that define phage growth are the generation time, fecundity and progeny survival frequency. A phage’s evolutionary history can be summarized as a series of responses to changes in the environmental constraints and opportunities. The objective of his work is to identify the general overlying principles of phage success so that these can serve as a guide for laboratory and in situ studies. André Comeau’s presentation focused on factors in the environment that substantially increase phage production. It was observed that sub-lethal doses of certain antibiotics stimulate virulent phage production in variety host-phage systems (e.g T4-E. coli system). The only common characteristic of these antibiotics is that they inhibit cell division. The fact that completely unrelated phages manifest this phenomenon suggests that it confers an important advantage to the phage. Nicholas Mann spoke about how phages influence environment by controlling the composition and dynamics of microbial populations and also the flux through the biogeochemical cycles. His study of a phage of an important component of the marine phytoplankton revealed some novel aspects of this phage-host relationship. A second theme of his research concerns the exploitation of phages to fight off bacterial infectious disease. He has isolated phages that infect and kill strains of MRSA, a serious human pathogen, and described their utility in therapy.
Sherwood Casjens’s discussed the virion assembly genes of phage P22, a Podoviridae distantly related to phage lambda. The morphogenesis genes of numerous P22-like phages were compared and although the genes have diverged substantially, the gene order is maintained. The evolution of these genes was analyzed in view of structure of the P22 virion and the constituent proteins. A recent invasion of genes in the P22-like phages replaced some ancestral morphogenesis genes by analogues. Jonathan Filée presented data on the islands of bacterial-type genes located within the genomes of giant Eukaryotic viruses. Such bacterial-like sequences include prokaryotic mobile elements that may have mediated the acquisition of these blocks of bacterial sequences. He described the extraordinarily diversity of the T4-like marine phages that are found in a variety of biotopes. Phylogenetic analysis of these T4-like phages revealed both a conserved viral “core” and a series of hypervariable segments that have been acquired by lateral gene transfer from alien phage and bacteria. Debbie Lindell studied the pattern of transcription during infection of the marine cyanobacterium Prochlorococcus by a T7-like podovirus P-SSP7. During phage infection three clusters of genes with different transcription patterns could be distinguished. Although the expression of most host genes declined after infection, the expression of some host genes increased. Many of these phage-induced host genes are located in islands in the bacterial genome that may be the consequence result of lateral gene transfer of phage origin.
Mya Breitbart made the point that viruses represent the largest reservoir of unknown sequence in the biosphere. Her metagenomic analysis of uncultured viral communities provides insights into the identity, diversity, and geographical distribution of these viruses. Her studies are aimed at quantifying this viral diversity, at identifying the features that distinguish viruses from different environments and at examining the evolutionary relationships between these viruses. Graham Hatfull presented the comparison of the genome sequences of 30 mycophages. Although, in general, they diverge at the sequence level, there were several of the phages were closely clustered to each other. These genomes have mosaic architectures and their constituent modules are generally small, frequently just a single gene. The ~3, 300 putative mycophage genes can be organized into ~1500 “phamilies” of sequences. The function of most of these “phamilies”, however, still remains obscure. Henry Krisch noted that only a minute fraction of the Biosphere’s phages have been studied. A large comparative genomic study was recently completed that focused on the T4-like phage family. All these phages have diverged from a distant ancestor and their genomes are partitioned into a conserved core of replication and morphogenesis genes and very plastic set of adaptive functions. Such partitioning could provide the flexibility for these phages to adapt to new environments while conserving a highly successful virion structure and replication apparatus.
Mike Dyall-Smith remarked that only a few viruses of extremely halophilic Archaea have been studied. The major barrier to such studies is the difficulties encountered in culturing many Archaeal host species. Recent technical developments have largely overcome such problems and the genome sequences of two new haloviruses with spindle and round morphotypes demonstrates that they both have terminal inverted repeats and terminal proteins and are thus likely to have an unusual mode of DNA replication involving protein priming. Patrick Forterre presented the current known diversity of plasmids and viruses of hyperthermophilic Archaea, as well as drew attention to the existence of vesicles containing DNA produced by a number of Archaea. These vesicles are relevant to microscopic observations of viral communities since these vesicles fluoresce in a fashion similar to viral particles. David Prangishvili continued by describing a series of double-stranded DNA viruses of hyperthermophilic Archaea. The bizarre morphotypes of some of these have not previously been encountered in dsDNA viruses. Their genome sequences are also odd, with more than 90% of the genes lacking any homologues in the database. The evolutionary origin of the viruses of hyperthermophilic Archaea may differ from that of other viruses. Curtis Suttle concluded that as the most basic and prevalent of the biosphere’s predators, viruses have been deeply implicated in defining the structure of life on our planet. Their long evolutionary history has generated a massive and largely unexplored reservoir of genetic diversity. Strikingly many environmental virus sequences have no known homologues, from this observation he concludes that much greater priority must be given to inventorying the virophere.
Harald Brüssow’s presentation dealt with phage predation of bacteria. When eukaryotic cells first evolved, bacteria had suddenly to confront a two front war to avoid becoming food for the new enemy, protists, or the old one, phage. Bacteria had to rapidly evolve countermeasures against both types of predation. He speculated that bacteria recruited and adapted genes from temperate phages to counteract the threat of ingestion by protists. Hence, it is hardly surprising that especially many pathogenic bacteria now use prophage-encoded genes for their defense against attack, for example, by phagocytes. Since escaping from the immune system is crucial to bacterial virulence, prophage genes could have similarly been co-opted to be evolutionary motor bacterial pathogenesis. Martha Clokie pointed out that much photosynthesis in oceans are carried out by cyanobacteria. Surprisingly these bacteria are frequently infected by phages that also contain, in their own genomes, copies of the core photosystem genes psbA and psbD. These genes were most probably acquired by lateral gene transfer from their hosts. They are expressed in infected cells grown in optimal light and nutrient conditions. These genes are also expressed under conditions similar to those of oligotrophic oceanic regions where cyanobacteria abound. Christine Jessup observed that organisms continually confront evolutionary trade-offs. One such trade-off is between an organism’s competitive ability and its resistance to predators and pathogens. Laboratory reconstructions involving bacteria and phage offer a powerful tool to investigate the consequences of such trade-offs. These simple model systems could provide important and general insights on how predator-prey interactions evolved. Ruth-Anne Sandaa has studied the link between viruses and their hosts in marine environments by employing synchronous viral culture and studying algal/bacterial dynamics. Such studies indicate that viruses may regulate the abundance of the dominant competitors and allow less predominant organisms to maintain this status stably. In addition, she described the prevalence of the phoH gene in viruses from marine habitats and suggested that this gene increased viral production. Eric Wommack noted that aside from aquatic environments, we understand remarkably little about the viral communities in the rest of the biosphere. For example, soils are inhabited by extraordinarily abundant viral communities which contain a surprising large proportion of temperate phages. In marked contrast to aquatic ecosystems, within soils the ratio of the abundances of viruses to bacteria is much more variable, ranging from ~10 in temperate forests to >3000 in the Antarctic dry valleys. Surprisingly, metagenomic sequence data indicates that soil viruses apparently share little genetic homology with their aquatic cousins.
Also in attendance: Anna Kuchment, journalist (general editor of Newsweek) and author on phage therapy.