Author: Ada Hagan
Editors: Patricia Garay, Ellyn Schinke, Irene Park
In “Virus vs Bacteria: Mortal combat” we learned that bacteriophage (phage) are a group of viruses that literally prey on bacteria and archaea. Phage fill a predatory role in their native ecosystems, helping to keep prey populations in check, in turn preventing exhaustion of available resources. We also explored in “Virus vs Bacteria: Enemy of my enemy” how humans can exploit these bacterial predators to be useful in a number of ways. But there’s quite a bit more to phage than meets the eye. New research is beginning to show us additional ecological impacts phage have on their environments—ones that can play a role in challenges humans face such as climate change and antibiotic resistance.
Phage and climate change
Viruses outnumber bacteria in the ocean ten to one, with an estimated 1023 phage infections occurring per second. But determining the diversity of viruses present in a population is extremely difficult with genetic sequencing—a technique used extensively to explore bacterial microbiomes. Where all bacteria share a specific section of their genome that researcher use as a genetic barcode, viruses don’t, making viral identification by sequencing tricky. An inability to accurately identify viruses means an inability to measure viral diversity (i.e. the number of distinct groups in a population).
But by sequencing viral DNA isolated from samples from Tara Ocean Project stations across the globe, Jennifer Brum has found more than 5,400 distinct viral populations and used their proteins (instead of genomes) to reliably identify more than 500,000 distinct groups of phage in the ocean. While the viral diversity was similar across samples and locations, there were particular phage groups that dominated number-wise in different environments. This pattern seemed to be dictated by ocean temperatures, particularly since samples from near the Antarctic had different viral diversity from the rest of the ocean.
Certain phage groups were present in all samples, so they were classified as “core” groups. Brum found that photic zones of the ocean, those upper regions that sunlight can reach, core phage groups are especially abundant. By comparison, the number of core phage groups detected decreases as the depth increases. Brum hypothesized that this decrease is because when viral particles sink from the photic zones to the ocean floor, they are detected in the lower ocean zones and the frequency of their detection dwindles as the depth increases.
And this is where climate change comes in.
The recycling of bacterial cell components—like amino acids, nucleic acids, and micronutrients (e.g., iron, calcium, and phosphate)—is linked to phage lysis of bacteria. The lysed cells tend to clump creating large, heavy particles. In most environments, this probably creates a closed loop where actively growing bacteria use resources scavenged from dead ones. In the ocean, however, these aggregated dead cells (with phage attached) sink, causing them to be detected in deeper ocean zones.
This same sedimentation carries the available cell components away from bacteria growing in the photic zones. To keep growing, photic microbes must to perform more photosynthesis, and use more atmospheric CO2, generating more O2, instead of recycling old cell components. This idea of carbon export by bacterial sedimentation was suggested as early as 1995, but Brum is one of the first to hypothesize that phage play a key role in the process.
Brum goes on to find specific viral populations that correlate with increased drawdown of CO2 in the ocean and tries to identify specific metabolic pathways that may increase bacterial CO2 use. By directly impacting the global carbon cycle, phage may also have an impact on climate change.
Phage and antibiotic resistance
Recent technological advances have made it possible for researchers to identify the types of bacteria, archaea, fungi, parasites, and viruses present in microbiomes. And by perturbing these ecosystems in controlled ways, researchers can also tease out information about how members of the community interact with each other and, in turn, what impact they may have on their environment, such as the human body.
The human body contains many different microbiomes on our skin, in our mouths, in our guts and under our nails. The viruses in each of these microbiomes make up the virome and includes both the viruses that infect human cells (e.g., herpes, and Epstein-Barr viruses) and bacteriophage. As researchers focus more on the virome, and the phage therein, they’ve learned a couple of things. First, that just like the bacteria in microbiomes, the phage populations reflect the body site from which they were sampled. That is to say, the virome of the mouth looks very different from the virome of the skin. Additionally, a large proportion of phage species (>70%) stick around over time, even if the bacterial population changes.
A 2015 study compared how the phage viromes of the mouth and the gut changed during a six-week exposure to antibiotics. The researchers found that the diversity of the viral populations stayed constant while the bacterial diversity changed considerably based on the type of antibiotic taken. Since antibiotics target bacteria, and phage prey on these bacteria, it isn’t entirely clear why the viral diversity does not change when the antibiotics alter the diversity of its prey.
Looking more closely at the viral sequences, the researchers realized that the phage genomes contained genes for antibiotic resistance. Additionally, the proportion of antibiotic resistance genes present increased slightly after antibiotic treatment, especially in the gut virome. Similar results have been found in mouse studies and suggests to researchers that the stability of the virome may contribute to maintaining antibiotic resistance.
Bacteriophage transduction. A phage infects a bacterium with its genome (1) and some of the bacterial genome is broken into smaller sections (2) that can be accidentally packaged into newly assembled phage (3). The phage containing sections of bacterial genomes then go on to infect new bacteria (4), injecting the bacterial genome instead of their own (5). Since the phage genome is missing, the phage can’t cause an active infection of the bacterial cell and instead the new DNA is added to the bacterium’s genome (6).
How does this work and what does this mean? Since phage genomes often insert into the genomes of their bacterial hosts, they occasionally package bacterial genes (like those responsible for antibiotic resistance) in addition to their own genomes when replicating. When these phage infect another bacterium, they can transfer the genes into a bacterium that may not have had them before. This process of gene transfer between bacteria via phage is called transduction. Because phage carrying antibiotic resistance genes are sticking around in microbiomes, even in people who haven’t taken antibiotics in years, there are many opportunities for them to transfer these genes to bacterial hosts. The hypothesis that phage might act as genetic reservoirs is relatively new and hasn’t been fully researched yet, but it could be a key factor in the spread of antibacterial resistance.
While phage have the potential to be quite useful to humans with phage therapies and nanotechnology, there’s much for us to learn about the many ways they impact their native ecosystems. These impacts may, or may not, always be positive for humans, but could give insight in addressing challenges humans face from climate change to antibiotic resistance.
Author’s note: This piece was adapted from two blog posts previously published on the American Society for Microbiology Microbial Science blog: “Exploring the human virome” and “Bacteriophage: A drop in the carbon ocean”
About the author
Ada Hagan is a doctoral student here at the University of Michigan in the department of Microbiology and Immunology. She does recon on the sneaky ways bacteria find nutrients (like iron!) when they are invading our bodies. Originally hailing from the mountains of East Tennessee, Ada earned both her B.S. and M.S. in Microbiology from East Tennessee State University. In her spare time, Ada spends time with her pets, husband, and new baby, and tries to fit in cooking, fishing & the occasional Netflix binge. Follow her on Twitter (@adahagan) and see more of her posts on LinkedIn.
Read more posts by Ada here.
Vibrio vulnificus – By CDC/James Gathany (PHIL #7815) – Obtained from the CDC Public Health Image Library, Public Domain, https://commons.wikimedia.org/w/index.php?curid=2740640
Bacteriophage transduction – By Reytan with modifications by Geni – modified version of Image: Transduction (genetics).svg, Public Domain, https://commons.wikimedia.org/w/index.php?curid=2123455