Bacteriophages are obligate parasites of bacteria characterized by the breadth of hosts that they can infect. This “host range” depends on the genotypes and morphologies of the phage and the bacterial host, but also on the environment in which they are interacting. Understanding phage host range is critical to predicting the impacts of these parasites in their natural host communities and their utility as therapeutic agents, but is also key to predicting how phages evolve and in doing so drive evolutionary change in their host populations, including through movement of genes among unrelated bacterial genomes. Here, we explore the drivers of phage infection and host range from the molecular underpinnings of the phage–host interaction to the ecological context in which they occur. We further evaluate the importance of intrinsic, transient, and environmental drivers shaping phage infection and replication, and discuss how each influences host range over evolutionary time. The host range of phages has great consequences in phage-based application strategies, as well as natural community dynamics, and we therefore highlight both recent developments and key open questions in the field as phage-based therapeutics come back into focus.
Gene Co-occurrence Networks Reflect Bacteriophage Ecology and Evolution
ABSTRACT Bacteriophages are the most abundant and diverse biological entities on the planet, and new phage genomes are being discovered at a rapid pace. As more phage genomes are published, new methods are needed for placing these genomes in an ecological and evolutionary context. Phages are difficult to study by phylogenetic methods, because they exchange genes regularly, and no single gene is conserved across all phages. Here, we demonstrate how gene-level networks can provide a high-resolution view of phage genetic diversity and offer a novel perspective on virus ecology. We focus our analyses on virus host range and show how network topology corresponds to host relatedness, how to find groups of genes with the strongest host-specific signatures, and how this perspective can complement phage host prediction tools. We discuss extensions of gene network analysis to predicting the emergence of phages on new hosts, as well as applications to features of phage biology beyond host range. IMPORTANCE Bacteriophages (phages) are viruses that infect bacteria, and they are critical drivers of bacterial evolution and community structure. It is generally difficult to study phages by using tree-based methods, because gene exchange is common, and no single gene is shared among all phages. Instead, networks offer a means to compare phages while placing them in a broader ecological and evolutionary context. In this work, we build a network that summarizes gene sharing across phages and test how a key constraint on phage ecology, host range, corresponds to the structure of the network. We find that the network reflects the relatedness among phage hosts, and phages with genes that are closer in the network are likelier to infect similar hosts. This approach can also be used to identify genes that affect host range, and we discuss possible extensions to analyze other aspects of viral ecology.
more »
« less
- Award ID(s):
- 1661357
- NSF-PAR ID:
- 10057265
- Date Published:
- Journal Name:
- mBio
- Volume:
- 9
- Issue:
- 2
- ISSN:
- 2150-7511
- Page Range / eLocation ID:
- e01870-17
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
more » « less
Abstract -
Imperiale, Michael J. (Ed.)ABSTRACT By entering a reversible state of reduced metabolic activity, dormant microorganisms are able to tolerate suboptimal conditions that would otherwise reduce their fitness. Dormancy may also benefit bacteria by serving as a refuge from parasitic infections. Here, we focus on dormancy in the Bacillota , where endospore development is transcriptionally regulated by the expression of sigma factors. A disruption of this process could influence the survivorship or reproduction of phages that infect spore-forming hosts with implications for coevolutionary dynamics. We characterized the distribution of sigma factors in over 4,000 genomes of diverse phages capable of infecting hosts that span the bacterial domain. From this, we identified homologs of sporulation-specific sigma factors in phages that infect spore-forming hosts. Unlike sigma factors required for phage reproduction, we provide evidence that sporulation-like sigma factors are nonessential for lytic infection. However, when expressed in the spore-forming Bacillus subtilis , some of these phage-derived sigma factors can activate the bacterial sporulation gene network and lead to a reduction in spore yield. Our findings suggest that the acquisition of host-like transcriptional regulators may allow phages to manipulate a complex and ancient trait in one of the most abundant cell types on Earth. IMPORTANCE As obligate parasites, phages exert strong top-down pressure on host populations with eco-evolutionary implications for community dynamics and ecosystem functioning. The process of phage infection, however, is constrained by bottom-up processes that influence the energetic and nutritional status of susceptible hosts. Many phages have acquired auxiliary genes from bacteria, which can be used to exploit host metabolism with consequences for phage fitness. In this study, we demonstrate that phages infecting spore-forming bacteria carry homologs of sigma factors, which their hosts use to orchestrate gene expression during spore development. By tapping into regulatory gene networks, phages may manipulate the physiology and survival strategies of nongrowing bacteria in ways that influence host-parasite coevolution.more » « less
-
more » « less
Abstract The rate and trajectory of evolution in an obligate parasite is critically dependent on those of its host(s). Adaptation to a genetically homogeneous host population should theoretically result in specialization, while adaptation to an evolving host population (i.e., coevolution) can result in various outcomes including diversification, range expansion, and/or local adaptation. For viruses of bacteria (bacteriophages, or phages), our understanding of how evolutionary history of the bacterial host(s) impacts viral genotypic and phenotypic evolution is currently limited. In this study, we used whole genome sequencing and two different metrics of phage impacts to compare the genotypes and phenotypes of lytic phages that had either coevolved with or were repeatedly passaged on an unchanging (ancestral) strain of the phytopathogen
Pseudomonas syringae . Genomes of coevolved phages had more mutations than those of phages passaged on a constant host, and most mutations were in genes encoding phage tail‐associated proteins. Phages from both passaging treatments shared some phenotypic outcomes, including range expansion and divergence across replicate populations, but coevolved phages were more efficient at reducing population growth (particularly of sympatric coevolved hosts). Genotypic similarity correlated with infectivity profile similarity in coevolved phages, but not in phages passaged on the ancestral host. Overall, while adaptation to either host type (coevolving or ancestral) led to divergence in phage tail proteins and infectivity patterns, coevolution led to more rapid molecular changes that increased bacterial killing efficiency and had more predictable effects on infectivity range. Together, these results underscore the important role of hosts in driving viral evolution and in shaping the genotype–phenotype relationship. -
Abstract Recent research has underscored the immense diversity and key biogeochemical roles of large DNA viruses in the ocean. Although they are important constituents of marine ecosystems, it is sometimes difficult to detect these viruses due to their large size and complex genomes. This is true for “jumbo” bacteriophages, which have genome sizes >200 kbp and large capsids reaching up to 0.45 µm in diameter. In this study, we sought to assess the genomic diversity and distribution of these bacteriophages in the ocean by generating and analyzing jumbo phage genomes from metagenomes. We recover 85 marine jumbo phages that ranged in size from 201 to 498 kilobases, and we examine their genetic similarities and biogeography together with a reference database of marine jumbo phage genomes. By analyzing Tara Oceans metagenomic data, we show that although most jumbo phages can be detected in a range of different size fractions, 17 of our bins tend to be found in those greater than 0.22 µm, potentially due to their large size. Our network-based analysis of gene-sharing patterns reveals that jumbo bacteriophages belong to five genome clusters that are typified by diverse replication strategies, genomic repertoires, and potential host ranges. Our analysis of jumbo phage distributions in the ocean reveals that depth is a major factor shaping their biogeography, with some phage genome clusters occurring preferentially in either surface or mesopelagic waters, respectively. Taken together, our findings indicate that jumbo phages are widespread community members in the ocean with complex genomic repertoires and ecological impacts that warrant further targeted investigation.more » « less
-
null (Ed.)Abstract CrAssphage is the most abundant human-associated virus and the founding member of a large group of bacteriophages, discovered in animal-associated and environmental metagenomes, that infect bacteria of the phylum Bacteroidetes. We analyze 4907 Circular Metagenome Assembled Genomes (cMAGs) of putative viruses from human gut microbiomes and identify nearly 600 genomes of crAss-like phages that account for nearly 87% of the DNA reads mapped to these cMAGs. Phylogenetic analysis of conserved genes demonstrates the monophyly of crAss-like phages, a putative virus order, and of 5 branches, potential families within that order, two of which have not been identified previously. The phage genomes in one of these families are almost twofold larger than the crAssphage genome (145-192 kilobases), with high density of self-splicing introns and inteins. Many crAss-like phages encode suppressor tRNAs that enable read-through of UGA or UAG stop-codons, mostly, in late phage genes. A distinct feature of the crAss-like phages is the recurrent switch of the phage DNA polymerase type between A and B families. Thus, comparative genomic analysis of the expanded assemblage of crAss-like phages reveals aspects of genome architecture and expression as well as phage biology that were not apparent from the previous work on phage genomics.more » « less
- Free Publicly Accessible Full Text
-
Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1128/mBio.01870-17
