Protein switch could aid battle against hospital infections

In work that could lead to new therapeutics to combat hospital-acquired infections, researchers have determined the structure and mechanism of action of the bacterial protein MgrA (Nat. Chem. Biol., DOI: 10.1038/nchembio820). Staphylococcus aureus accounts for most deaths associated with infections that some patients get while in hospitals. Its MgrA protein is known to regulate the pathogen's virulence, cell wall biosynthesis, metabolic changes, and antibiotic resistance, but it wasn't known how. Assistant professor of chemistry Chuan He of the University of Chicago and his coworkers obtained the crystal structure of the dimeric protein and have found that a key cysteine works like a switch, activating MgrA when the cysteine is oxidized. This MgrA activation causes the bacterium to thicken its cell wall, turn on a protective anaerobic metabolic pathway, shut down its virulence, and increase its antibiotic resistance. The researchers hope to come up with small molecules that turn on MgrA and thus render the bacterium harmless.