Viruses are infectious agents that depend on a host cell to reproduce. There are viruses that can infect pretty much every kind of cell, including bacterial cells. Viruses that infect bacteria are called bacteriophages. Research by scientists at the University of California, Berkeley has now revealed that bacteriophages (or phages) can take up residence in the human gut, where a massive community of microbes including trillions of bacteria lives. These bacteriophages are massive - roughly ten times larger than phages that have been found in people before, and they can devastate gut bacteria. The findings have been reported in Nature Microbiology.
"Phage are well-known to carry genes that cause disease and genes that code for antibiotic resistance," said Jill Banfield, the leader of the Innovative Genomics Institute's microbiology initiative, a UC Berkeley professor of earth and planetary science and of environmental science, policy, and management. "The movement of megaphages along with the movement of their host bacteria raises the possibility that disease also can move between animals and humans, and that the capacity for this is much larger with megaphage."
These bacteriophages were also identified in pig and baboon guts, indicating that bacteriophages, and the genes they carry, can move between species and potentially carry disease.
These megaphages also show that we still have a lot to learn about viruses, which seem to toe the line between living and non-living things. "These huge entities fill the gap between what we think of as non-life and life, and in a sense, we have mostly missed them," Banfield noted.
Banfield is a metagenomic sequencing pioneer. By using metagenomics tools to sequence all the genes contained within a mixture of organisms, she and her colleagues have revealed a tremendous number of new microbes in samples from geysers, mine runoff, and the human intestinal tract among other places. Some of those microbes carry remnants of phage genomes, which serve as reminders of past invaders and function as a kind of defense system. That phenomenon was utilized by other researchers that developed the CRISPR/Cas9 genome-editing tool. Learn more about how bacteria use CRISPR from the video.
In this study, Banfield revealed the megaphages while studying the intestinal flora of people in Bangladesh with colleagues. In one kind of gut microbe, Prevotella, the researchers found bits of megaphage DNA within a CRISPR segment. Prevotella is not usually found in people that consume a western diet, and it seems megaphages prey on gut microbes. Because upper respiratory infections and periodontal disease have been linked to Prevotella, a megaphage might be useful as a treatment for Prevotella-induced infections.
This group of newly found megaphages were called Lak phages; they were found in Laksam Upazila of Bangladesh. Researcher and study first author Audra Devoto also identified Lak phages in hunter-gatherers of Tanzania, as well as in two separate Kenyan baboon groups and in pigs on Danish farms.
"The Lak phages in the pig are more closely related to humans than baboons are, so it's quite probable that these phages are moving across animal cohorts," Banfield said. "We suspect that the Prevotella and the Lak phage were pretty recently acquired by the baboons, because the baboons have so little resistance to them and they are so widespread among them."
Phages can promote human illness, and phages have also been explored as a therapeutic. Banfield wants to know more about the genes that these phages carry, how phage and gut bacteria populations change with diet and time, and how health is affected.
"These genomes are full of proteins of unknown function, probably pathways for processes not even imagined to date. There is a lot of new biology to be discovered in these new genomes," she said.
The video above explains what metagenomics is.