Microbes & Hosts Fight to Acquire Essential Metals: This Battle May Open the Door for New Treatments

Every time that a bacterial infection occurs within an individual, microbes and hosts engage in a persistent battle over precious metals, such as iron. The host struggles to keep these essential metals away from the microbes, which need them for their survival. In this battle, both the host and the microbes release a number of molecules and proteins. Researchers, such as Elizabeth Nolan, PhD, an associate professor of chemistry at the Massachusetts Institute of Technology (MIT), hope that further analysis of this struggle will provide insight that may help inform the development of new drugs that can be used in the fight against bacterial infections.

In a recent press release, Dr. Nolan explained, “Understanding how our innate immune system works is important for thinking about the development of new ways to treat infectious diseases.”

Essential metals such as iron, calcium, magnesium, and zinc assist cells in performing a variety of functions, such as, “cell respiration, catalyzing chemical reactions, signal transduction, and maintaining structural integrity of proteins and nucleic acids.” In fact, 30% of cell proteins need assistance from the aforementioned metals.

Dr. Nolan, head of the Nolan Lab at MIT, created a research program that would focus on how microbes and hosts fight for these essential metals. One of her team’s projects specifically focused on siderophores, which are molecules that bacteria use as a tool to extract essential metals from hosts. These siderophores, once released into their environment, actually adhere to the essential metals and then bring them back into bacterial cells.

The team sought to take a closer look at this extraction process to see if further understanding could inform potential therapeutic avenues. They intervened on this process by using these molecules to bring antibiotics back into bacterial cells instead. Dr. Nolan and her team found that by doing this, they could avoid killing microbe species that are actually beneficial; by adhering antibiotics to specific siderophores, only certain bacterial strains are targeted, and thus, only harmful microbes would be eliminated.

This isn’t the only time that Dr. Nolan and her team used Salmonella siderophores to increase their understanding. In another past study, the researchers found a new way to “immunize against microbes that invade the gastrointestinal tract,” in mice.

According to the press release, the researchers “targeted a molecule that Salmonella and other bacteria secrete to scavenge iron.” They found that, “immunization against this molecule” decreased growth of Salmonella thanks to a number of antibodies that had been created during the immunization process. Not only did this process reduce growth, but it also resulted in “much lower levels of the bacteria.”

An approach like this may have the potential to substitute for antibiotic use, which is needed in a world that is experiencing increased antibiotic resistance. According to Dr. Nolan, “We have a huge problem in terms of infectious disease and antibiotic resistance. One aspect we like about our strategy is that it’s narrow-spectrum, in contrast to many small-molecule antibiotics that are broad-spectrum and can disrupt the commensal [beneficial] microbiota, which can then have secondary negative consequences for the patient.”

In addition to her work with siderophores, Dr. Nolan has also examined the different proteins that both mammals and humans alike use in defense against potential bacterial infection. One such defensive protein is calprotectin, a protein that prevents microbes from obtaining essential metals by “scavenging” for them itself. The researchers found, back in 2015, that calprotectin can actually withhold iron, and by doing so, it keeps the essential metal away from harmful microbes that need it to survive and grow.

These findings and future research work toward a common goal: to be better prepared when it comes to bacterial infections. Through the creation of new strategies that are narrow-spectrum, researchers are working to better fight against these harmful infections and lessen the risk of these pathogens developing resistance to antibiotics.