Iron treatment helps infected mice survive without killing bacteria

Two mice receive the same deadly infection. One lives; the other dies. At the Salk Institute, HHMI Investigator Janelle Ayres and her lab found that the deciding factor was not the amount of bacteria in the body, but how the host responded to the damage caused by infection.

The team studied Citrobacter rodentium, a gut-dwelling pathogen. At the dose used, about half the mice normally survived. When researchers gave the animals an iron supplement alongside the infection, 100% survived. The protection remained even when the mice received 10, 100 or 1,000 times the bacterial dose that was normally fatal.

Iron did not kill the bacteria or reduce their pathogen burden. Instead, it triggered metabolic changes that made more glucose available, the bacteria’s preferred food. Sensing that abundance, the microbes reduced their virulence; over time, they evolved mutations that permanently deleted their disease-causing genes. Ayres describes the result as a shift toward commensalism: the pathogen persists without harming its host.

The work also exposed a danger in treating infection as a one-size-fits-all problem. In experiments with bacteria that commonly cause sepsis, young and old mice carried the same pathogen burden but showed different heart responses. Two genes, Foxo1 and Trim63, protected young survivors from damaging heart growth, yet drove illness and death in older mice. A cardiac pattern that killed young mice was associated with recovery in aged animals.

So what changes, concretely? The research points to a second treatment strategy alongside antibiotics: protect the body from infection damage while altering conditions that make microbes dangerous. That could eventually support treatments less likely to fuel antibiotic resistance. But the evidence remains in mice; Ayres says a therapy aimed at these genes could help a young sepsis patient and harm an elderly one if the mechanism carries over to humans.