Co-evolution Of Phages Research Articles

Rapidly fluctuating environments constrain coevolutionary arms races by impeding selective sweeps

Although pervasive, the impact of temporal environmental heterogeneity on coevolutionary processes is poorly understood. Productivity is a key temporally heterogeneous variable, and increasing productivity has been shown to increase rates of antagonistic arms race coevolution, and lead to the evolution of more broadly resistant hosts and more broadly infectious parasites. We investigated the effects of the grain of environmental heterogeneity, in terms of fluctuations in productivity, on bacteria–phage coevolution. Our findings demonstrate that environmental heterogeneity could constrain antagonistic coevolution, but that its effect was dependent upon the grain of heterogeneity, such that both the rate and extent of coevolution were most strongly limited in fine-grained, rapidly fluctuating heterogeneous environments. We further demonstrate that rapid environmental fluctuations were likely to have impeded selective sweeps of resistance alleles, which occurred over longer durations than the fastest, but not the slowest, frequency of fluctuations used. Taken together our results suggest that fine-grained environmental heterogeneity constrained the coevolutionary arms race by impeding selective sweeps.

Physical model of the immune response of bacteria against bacteriophage through the adaptive CRISPR-Cas immune system

Bacteria and archaea have evolved an adaptive, heritable immune system that recognizes and protects against viruses or plasmids. This system, known as the CRISPR-Cas system, allows the host to recognize and incorporate short foreign DNA or RNA sequences, called ‘spacers’ into its CRISPR system. Spacers in the CRISPR system provide a record of the history of bacteria and phage coevolution. We use a physical model to study the dynamics of this coevolution as it evolves stochastically over time. We focus on the impact of mutation and recombination on bacteria and phage evolution and evasion. We discuss the effect of different spacer deletion mechanisms on the coevolutionary dynamics. We make predictions about bacteria and phage population growth, spacer diversity within the CRISPR locus, and spacer protection against the phage population.

Phage-induced diversification improves host evolvability

BackgroundBacteriophage (viruses that infect bacteria) are of key importance in ecological processes at scales from biofilms to biogeochemical cycles. Close interaction can lead to antagonistic coevolution of phage and their hosts. Selection pressures imposed by phage are often frequency-dependent, such that rare phenotypes are favoured; this occurs when infection depends on some form of genetic matching. Also, resistance to phage often affects host fitness by pleiotropy (whereby mutations conferring resistance affect the function of other traits) and/or direct costs of resistance mechanisms.ResultsHere a simple model of bacteria and bacteriophage coevolving in a resource-limited chemostat is used to study the effect of coevolving phage on the evolution of bacterial hosts. Density-dependent mortality from phage predation limits the density of any single bacterial strain, preventing competitive exclusion by faster-growing strains. Thus multiple strains can coexist by partitioning resources and stable high diversity is created by negative frequency-dependent selection from phage. Standing bacterial diversity promotes adaptation in dynamic environments, since it increases the likelihood of a pre-existing genotype being suited to altered conditions. In addition, frequency-dependent selection for resistance creates transient local trade-offs between growth rate and resistance that allow bacterial strains to adapt across fitness valleys. Thus bacterial populations that (in the absence of phage) would have been trapped at sub-optimal local peaks in the adaptive landscape are able (in the presence of phage) to reach alternate higher peaks than could have been reached by mutation alone.ConclusionsThis study shows that reasonable assumptions for coevolution of bacteria and phage create conditions in which phage increase the evolutionary potential of their hosts. Thus phage, in contrast to their deleterious effects on individual host cells, can confer an evolutionary benefit to bacterial populations. These findings have implications for the role of phage in ecosystem processes, where they have mainly been considered as a mortality factor; these results suggest that on long timescales phage may actually increase bacterial productivity by aiding the evolution of faster-growing strains. Furthermore, these results suggest that the therapeutic use of phage to treat bacterial infections (phage therapy) could have unintended negative side-effects.

Bacteriophage genes that inactivate the CRISPR/Cas bacterial immune system.

A widespread system used by bacteria for protection against potentially dangerous foreign DNA molecules consists of the clustered regularly interspaced short palindromic repeats (CRISPR) coupled with cas (CRISPR-associated) genes. Similar to RNA interference in eukaryotes, these CRISPR/Cas systems use small RNAs for sequence-specific detection and neutralization of invading genomes. Here we describe the first examples of genes that mediate the inhibition of a CRISPR/Cas system. Five distinct 'anti-CRISPR' genes were found in the genomes of bacteriophages infecting Pseudomonas aeruginosa. Mutation of the anti-CRISPR gene of a phage rendered it unable to infect bacteria with a functional CRISPR/Cas system, and the addition of the same gene to the genome of a CRISPR/Cas-targeted phage allowed it to evade the CRISPR/Cas system. Phage-encoded anti-CRISPR genes may represent a widespread mechanism for phages to overcome the highly prevalent CRISPR/Cas systems. The existence of anti-CRISPR genes presents new avenues for the elucidation of CRISPR/Cas functional mechanisms and provides new insight into the co-evolution of phages and bacteria.

Existence of Separate Domains in Lysin PlyG for Recognizing Bacillus anthracis Spores and Vegetative Cells

As a potential antimicrobial, the bacteriophage lysin PlyG has been reported to specifically recognize Bacillus anthracis vegetative cells only and to kill B. anthracis vegetative cells and its germinating spores. However, how PlyG interacts with B. anthracis spores remains unclear. Herein, a 60-amino-acid domain in PlyG (residues 106 to 165), located mainly in the previously identified catalytic domain, was found able to specifically recognize B. anthracis spores but not vegetative cells. The exosporium of the spores was found to be the most probable binding target of this domain. This is the first time that a lysin for spore-forming bacteria has been found to have separate domains to recognize spores and vegetative cells, which might help in understanding the coevolution of phages with spore-forming bacteria. Besides providing new biomarkers for developing better assays for identifying B. anthracis spores, the newly found domain may be helpful in developing PlyG as a preventive antibiotic to reduce the threat of anthrax in suspected exposures to B. anthracis spores.

Marine Viruses Exploit Their Host's Two-Component Regulatory System in Response to Resource Limitation

Phosphorus (P) availability, which often limits productivity in marine ecosystems, shapes the P-acquisition gene content of the marine cyanobacteria Prochlorococcus [1-4] and its viruses (cyanophages). As in other bacteria, in Prochlorococcus these genes are regulated by the PhoR/PhoB two-component regulatory system that is used to sense and respond to P availability and is typical of signal transduction systems found in diverse organisms. Replication of cyanophage genomes requires a significant amount of P, and therefore these phages could gain a fitness advantage by influencing host P acquisition in P-limited environments. Here we show that the transcription of a phage-encoded high-affinity phosphate-binding protein gene (pstS) and alkaline phosphatase gene (phoA)-both of which have host orthologs-is elevated when the phages are infecting host cells that are P starved, relative to P-replete control cells. We further show that the phage versions of these genes are regulated by the host's PhoR/PhoB system. This not only extends this fundamental signaling mechanism to viruses but is also the first example of regulation of lytic phage genes by nutrient limitation in the host. As such, it reveals an important new dimension of the intimate coevolution of phage, host, and environment in the world's oceans.

Insertion of host DNA into PVL-encoding phages of the Staphylococcus aureus lineage ST80 by intra-chromosomal recombination

Temperate bacteriophages play a critical role in the pathogenicity of the human pathogen Staphylococcus aureus by mediating positive lysogenic conversion for different virulence factors such as Panton-Valentine leukocidin (PVL) or by interrupting chromosomal virulence genes. PVL-encoding phages are integrated in the S. aureus genome within a conserved ORF which is surrounded by a cluster of tandemly repeated genes. Here we demonstrate that in S. aureus clonal complex ST80 strains PVL-phage induction led to the acquisition of host DNA into the phage genome probably due to a homologous recombination event between direct repeats of the two paralogous genes adjacent to the phage integration site. Phage excision was accompanied by an additional chromosomal deletion in this region. This so far unrecognized mechanism of DNA uptake into the phage genome may play an important role in the co-evolution of phages and bacteria.

The Cyanophage Molecular Mixing Bowl of Photosynthesis Genes

The Cyanophage Molecular Mixing Bowl of Photosynthesis Genes