In an era of increasing concern about the prevalence of antibiotic-resistant illness, Case Western Reserve researchers have identified a promising new pathway to disabling disease: blocking bacteria's access to iron in the body.
The scientists showed how bacterial siderophore, a small molecule, captures iron from two abundant supply sources to fan bacterial growth as well as how the body launches a chemical counterassault against this infection process. Their findings appear in a recent edition of The Journal of Experimental Medicine.
"Bacterial siderophore will be an important target for therapeutics one day because it can be modified to prevent bacteria from acquiring iron, but at the same time, it's possible to preserve host access to iron," said senior author Laxminarayana Devireddy, DVM, PhD, assistant professor of pathology, Case Comprehensive Cancer Center.
Investigators knew from the outset that bacterial siderophore captures iron from the host mammal and transforms it so that bacteria can absorb and metabolize the mineral. In this investigation, Devireddy and his colleagues discovered that human mitochondria, which very closely resemble bacteria, possess their own iron-acquisition machinery mitochondrial siderophore. Mammalian mitochondria are membrane-encased subunits within cells that generate most of the cell's energy, and like their bacteria counterparts, mammalian mitochondria have their own siderophore mechanism that seeks out, captures and delivers iron for utilization.
At the test tube level, investigators found that bacteria can feed on iron supplied by bacterial siderophore and mitochondrial siderophore. From this glut of iron, bacteria proliferate and make the host mammal very ill with an infection.
"It's like bacteria can use their own iron-capture machinery or the host's. It just doesn't matter," Devireddy said. "They are very good at utilizing siderophore from both bacterial and mammal
|Contact: Jeannette Spalding|
Case Western Reserve University