Living Organisms Depend on Bacterial Production of Critical Vitamin B12

All living organisms need a little bit of it to form red blood cells and DNA, as well as to build and support brain and nerve cells. But it's hard to come by: Humans don't make it. Animals don't make it. Plants don't make it.

In fact, this essential nutrient is made exclusively by certain bacteria and archaea.

But we've got to have it, so we scavenge.

Humans tap natural food sources such as meat, shellfish, fish, poultry, and dairy, as well as supplements, to get what we need. 

Scientists have a clear picture of how B12 is absorbed into the body. What is harder to understand is how and why those elite microbial B12 producers allow their precious stock to become available to the broader microbial community in the first place.

In a paper published recently in the ISME Journal, Virginia Tech biologist Bryan Hsu and collaborators revealed the mechanism for B12 release: plundering by bacteria-eating viruses called bacteriophages, or phages.

Phages are viruses that infect only bacteria. Although they are ecologically entrenched with bacteria, phages are harder to classify and more mysterious. Hsu, the Blackwood Junior Faculty Fellow in the College of Science, studies how phages shape the gut microbiome.

Phages attack bacteria in a gruesome process called lysing. The virus attaches to a bacterial cell, injects its own DNA, and reprograms the host cell to manufacture more phages. When the bacterial cell eventually succumbs, it explodes into a flood of new phages. But there's more than just new phages in the bacterial death gush.

It has all the DNA, the protein, sugars - all these things that the bacterial cell normally hoards so that it can continue to grow."

Bryan Hsu, Biologist, Virginia Tech  

It also includes vitamin B12.

In the paper, Hsu's research team demonstrated that phage infection is a primary driver for releasing B12. David da Silva Barreira, the study's first author and a former Virginia Tech postdoctoral associate, verified this by co-culturing a B12 producer with a B12 consumer that needs to scavenge for B12 from the environment.

Without introducing the phage, the B12 user didn't grow. It couldn't get to the B12, and the nutrient remained trapped inside the intact producer cell.

But then they unleashed the phages to lyse the producer, and the consumer began to thrive. 

"In a genetically well-defined system, we can demonstrate that phage is necessary," said Hsu. "The B12 doesn't just leak out."

To confirm that B12 specifically drove the growth boost - rather than other cellular contents - da Silva Barreira repeated the experiment with a producer strain genetically engineered to lack B12. When phages lysed the modified cell, the user failed to grow. The result proved that B12 was the essential component - a first for the field.

To test whether the findings held up in a more complex environment, the researchers conducted similar experiments on major types of gut bacteria found in the human digestive tract. Microbes dependent on B12 grew only when a phage lysed a B12 producer.

Taken together, these findings suggest that the brutal methods of bacteriophages play a critical role in distributing nutrients, promoting microbial diversity, and supporting microbiome gut health.