From our nose to our lungs to our guts, the human body is home to a diverse range of microorganisms. Such rich microbial ecosystems are prime hunting grounds for viruses that infect and kill bacteria. But how these bacteria-killing viruses interact with human cells has remained mysterious.
Past research has shown that human cells can slurp up bacteria-killing viruses when a cell ingests a large amount of the fluid surrounding it. Microbiologist Jeremy Barr wanted to know if the ingested viruses have any effect on the cell’s immune response.
To his surprise, Barr instead found that mammalian cancer cells grown in the lab use the viruses as a food source. The results, published in the Oct. 26 PLOS Biology, show that it’s possible for mammalian cells to use bacteria-killing viruses as fuel — meaning normal, noncancerous cells could do it too, though this remains to be seen.
This nascent line of work upends traditional biological dogma, says Barr of Monash University in Melbourne, Australia. “You’re told that [phages] just do not interact with mammalian cells,” he says. “And that’s completely false. They do.”
Bacteria-killing viruses, called bacteriophages, are ubiquitous in the human body. Cells in our body ingest up to 30 billion phages each day, Barr estimates. To test how the phages interact with mammalian cells, the researchers experimented with human and dog cancer cells, mainly because they are easy to cultivate in the lab. The team grew the cancer cells in an environment flush with bacteriophage T4, a common virus that preys on E. coli.
Barr’s team then used a battery of antibodies, each of which binds to a specific type of protein, to determine the proteins the cells made in response to the phage. Though the researchers expected to see more proteins involved in inflammation, part of the cell’s immune response, they instead saw changes in the amounts of proteins involved in cell growth and division. “Cells that had been given phage were actually growing at a faster rate,” Barr says. This suggests that “they’re using the phages as a food source.”
Because the cells used in this study were grown in a lab and come from established lines of cells used for research, we can’t yet be sure that cells in the bodies of humans and other mammals behave the same way, says Paul Bollyky, an immunologist at Stanford University. “Cell lines are funny creatures,” he says. “They do things energetically that are probably closer to tumor biology than to normal cell biology, so it can be difficult to extrapolate.”
Still, “this is a really exciting and trailblazing study from a group that’s doing excellent work,” Bollyky says. “Like a lot of good science, this study really raises questions.”
Barr says he next wants to investigate whether noncancerous cells derived from a living animal also snack on phages. He also plans to examine more phages, especially viruses that — like T4 — live in our guts, and others that are being used in phage therapy, where viruses are used instead of antibiotics to kill infectious bacteria (SN: 12/14/21). “We know they kill the bacterial hosts, but what are they doing to the human host?” Barr asks. “How do they interact?”