One of the ways humans combat invading pathogens – such as Staphylococcus aureus (“staph”) – is by hiding nutrients that are essential to their growth.
Eric Skaar, associate professor of pathology, microbiology and immunology, Walter Chazin, Chancellor’s Chair in Medicine and professor of microbiology, and colleagues previously demonstrated that the protein calprotectin sequesters manganese and zinc and inhibits staph growth. Now, the team has discovered that by binding manganese, calprotectin inhibits staph’s defenses against superoxide, a toxic compound that the immune system uses to destroy microbes. They found that calprotectin increases superoxide levels and enhances the ability of neutrophils (immune cells) to kill staph. The researchers also showed that calprotectin’s metal binding is essential to its antimicrobial properties.
Because similar superoxide defense systems are found in a wide range of bacterial pathogens, calprotectin may also enhance the sensitivity of those microbes to superoxide. The findings, reported Aug. 18 in Cell Host & Microbe, suggest that it may be possible to develop therapeutics that kill microbes by starving them of essential nutrients.
This research was supported by the National Institute of Allergy and Infectious Diseases and the National Institute of General Medical Sciences.