Ashley Yeager in The Scientist:
About a year ago, some—but not all—of the mice in Janelle Ayres’s lab at the Salk Institute for Biological Studies in La Jolla, California, got really sick. Ayres and her colleagues had infected each of the animals with the pathogenic bacterium Citrobacter rodentium, and within a few days, some of the mice began losing weight. Their colons became severely inflamed, and the animals died not long after. But other mice that were also exposed to the bacterium looked perfectly healthy. All the mice were genetically identical. They were fed the same food, kept in the same kinds of cages, and had no notable differences in the composition of their microbiomes. “Yet half the animals died, and the other half survived,” exactly what she was aiming for, Ayres tells The Scientist.
…To try to understand what saved the survivors, Ayres and her colleagues examined the genes turned on in the mice’s livers, an organ that plays a major role in secreting signaling molecules to maintain homeostasis in the body. Compared with mice that died from the infection, the mice that survived expressed lots of genes linked with metabolizing iron. This indicated to Ayres that iron might help the animals cope with the infection, so she and her team decided to treat mice that were on the verge of dying from the C. rodentium infection with an iron supplement. The animals recovered. Intrigued, the team upped the stakes. They infected another set of mice with a dose of the bacterium that should kill all of the animals, not just half of them—then gave the animals iron. All of the mice survived. Still not satisfied, Ayres and her team infected a new set of mice with 1,000 times the lethal dose of the bacterium, followed by iron. “They were perfectly fine,” Ayres says, while infected mice not getting the iron supplement died within days.1
Sequencing the genomes of C. rodentium in the control and iron-fortified mice revealed that the bacterium in the mice fed iron had accumulated mutations that tamped down expression of multiple genes for proteins in a virulence pathway, disabling its ability to cause disease. The bacteria, found in the colon, were, in essence, “just part of the [mice’s] microbiome now,” Ayres says.