Scientists at Kansas State University say they have discovered a family of proteins that could lead to better treatments for Staphylococcus aureus, a pathogenic bacterium that can cause more than 60,000 potentially life-threatening infections each year.
While S. aureus is typically a harmless commensal organism found in the nose and skin of 30% of the human population, it can cause serious and deadly infections if it invades deeper tissues. In their latest research study ("Staphylococcus aureus secretes a unique class of neutrophil serine protease inhibitors"), published in PNAS, Brian Geisbrecht, Ph.D., professor of biochemistry and molecular biophysics, and Kasra Ramyar, Ph.D., his research associate, and collaborators discovered that S. aureus secretes a family of proteins that prevent neutrophil serine proteases, or NSPs, from functioning, which is an important finding for understanding how infections are established. Neutrophils help prevent serious infections from occurring.
"Neutrophils are like the fire department of the immune system," said Dr. Geisbrecht. "They are the first on the scene when a microbial infection tries to take hold."
Neutrophils directly attack pathogens and emit biochemical signals that recruit other inflammatory immune cells to the site of infection when they release NSPs from intracellular granules.
"To our knowledge, Staph is the first example of any bacterium that secretes protease inhibitors specifically to block an aspect of the host immune response that is essential for its removal from the body," added Dr. Geisbrecht.
"S. aureus secretes a family of proteins that potently inhibits the activity of neutrophil serine proteases (NSPs): neutrophil elastase (NE), proteinase 3, and cathepsin G," wrote the investigators. "The NSPs, but not related serine proteases, are specifically blocked by the extracellular adherence protein (Eap) and the functionally orphan Eap homologs EapH1 and EapH2, with inhibitory-constant values in the low-nanomolar range."
The research may lead to better treatments for inflammatory conditions, such as emphysema and chronic obstructive pulmonary disease, which are the result of dysregulated neutrophil activation in the lung. The discovery that S. aureus secretes Eaps that block NSPs could eventually affect how staph infections are treated in the clinic.
"Understanding this interaction can not only help us design better therapies in the future, but may help make current treatment regimens work better," said Dr. Geisbrecht.