Mining the human microbiota for metallophores

The human microbiota includes hundreds of species and thousands of strains of microbes that must co-exist with each other and the human host. Key metal micronutrients that both the host and members of the microbiota require include iron, copper, zinc, manganese, molybdenum and nickel. The availability of these metals varies depending on the body site, diet, and health status.

This project has the potential to make broad and lasting impacts on our understanding of human-associated microbes by discovering the mechanisms by which these organisms acquire metals. One of the best described mechanisms for microbes to acquire metals is the use of siderophores (Greek for iron-bearers). These molecules have a high affinity for iron and are secreted outside the cell, have a high affinity for ferric iron, and are then selectively reabsorbed by the producing organism with the iron bound. There is increasing evidence that these molecules play a role not only in iron acquisition, but also in chelating other metal micronutrients leading to the proposal that many siderophores are actually “metallophores.”

This project will generate new knowledge about the importance of controlling the homeostasis of metal micronutrients to the health and stability of the human microbiota and likely change our thinking about the importance of metallophores within the framework of microbial communities. An additional value of this project is the potential to discover novel chemistry in the pathways of synthesis of metallophores, which can also be used for synthetic biology purposes to make new drugs or antibiotics to improve human health.

PRINCIPAL INVESTIGATOR
Michael Thomas, professor of bacteriology

CO-PRINCIPAL INVESTIGATORS
Federico Rey, associate professor of bacteriology

Timothy Bugni, professor of pharmacy