Around 20 percent of all humans are persistently colonized with Staphylococcus aureus bacteria, a leading cause of skin infections and one of the major sources of hospital-acquired infections, including the antibiotic-resistant strain MRSA.
University of Chicago scientists have recently discovered one of the keys to the immense success of S. aureusthe ability to hijack a primary human immune defense mechanism and use it to destroy white blood cells. The study was published Nov 15 in Science.
"These bacteria have endowed themselves with weapons to not only anticipate every immune defense, but turn these immune defenses against the host as well," said Olaf Schneewind, MD, PhD, professor and chair of the Department of Microbiology at the University of Chicago and senior author of the paper.
One of the first lines of defense in the human immune response are neutrophils, a type of white blood cell that ensnares invaders in neutrophil extracellular traps (NETs), a web-like structure of DNA and proteins. Captured bacteria are then destroyed by amoeba-like white blood cells known as macrophages. However, S. aureus infection sites are often marked by an absence of macrophages, indicating the bacteria somehow defend themselves against the immune system.
To reveal how these bacteria circumvent the human immune response, Schneewind and his team screened a series of S. aureus possessing mutations that shut down genes thought to play a role in infection. They looked to see how these mutated bacteria behaved in live tissue, and identified two strains that were unable to avoid macrophage attack. When these mutationsto the staphylococcal nuclease (nuc) and adenosine synthase A (adsA) genes respectivelywere reversed, infection sites were free of macrophages again.
Looking for a mechanism of action, the researchers grew S. aureus in a laboratory dish alongside neutrophils and macrophages. The
|Contact: Kevin Jiang|
University of Chicago Medical Center