Researchers at the Salk Institute report that giving mice dietary iron supplements enabled them to survive a normally lethal bacterial infection. This technique, which shifts the relationship between patients and pathogens away from antagonism and toward cooperation could present a new way of thinking about treatment options for pathogens. The findings are detailed in the journal Cell.
In the current study, the team studied a naturally occurring gastrointestinal infection in mice called by Citobacter rodentium (CR), which leads to diarrhea, weight loss and death in extreme cases. The team administered the lethal dose 50 (LD50) of the bacteria to the mice, observing the differences between the infected healthy population compared to the infected sick population and the uninfected healthy mice. This led to the observation that host iron metabolism was increased in the infected healthy population.
To test the association of iron metabolism in healthy, infected mice, the researchers administered the LD100 dose of Citrobacter to a population of mice and fed half the mice a normal diet and the other half a diet supplemented with iron for 14 days, after which they were returned to a normal diet. After the 20th day, all of the infected mice in the no-iron group had died as expected, but 100% of the iron supplement group were alive. This was in spite of both groups of mice having similar levels of bacteria. The findings held true even if the mice were given 100 times the LD100 course.
Further analysis revealed the course of dietary iron caused acute insulin resistance in the mice, thus reducing the amount of glucose absorbed from the intestine and increasing the amount of sugar available for the pathogen to metabolize. This prevented the bacteria from turning on genes that cause disease. Direct supplementation with glucose also gave the same result.
Following up a year later, the team found that the infected, healthy mice were still infected with Citrobacter, indicating the pathogen had become attenuated. Sequencing Citrobacter genomes isolated from these animals revealed the bacteria had accumulated mutations to render their pathogenic genes non-functional, causing increased cooperation.
The team warns that dietary iron is not necessarily a good idea for all infectious diseases, however they believe the potentially beneficial role cooperative defense systems. In the future, the group plans to explore if weakened bacterial vaccines could act as a type of live vaccine or whether there is possibility of reverting to virulence or lethality.