Stripping Staph Of its 'Golden Armor'

More people die from drug-resistant staph infections in the U.S. than from HIV/AIDS, so finding new antistaph strategies is an important research goal. Eric Oldfield at the University of Illinois, Urbana-Champaign, and colleagues have now identified such an approach by potently inhibiting formation of the golden pigment staphyloxanthin in Staphylococcus aureus, increasing the bacterium's susceptibility to attack by the human immune system (Science, DOI: 10.1126/science.1153018). They find that three phosphonosulfonate compounds disable the enzyme that makes dehydrosqualene, the first step to the pigment. One of the three phosphonosulfonates (shown) has been tested in human clinical trials as a cholesterol-lowering drug. For that application, it targets human squalene synthase, which catalyzes the initial step to cholesterol and is structurally similar to the enzyme target in S. aureus. Staph cells treated with the inhibitor grow white and become susceptible to attack by reactive oxygen species, a key tactic of the immune system's defense. Dosing mice with the inhibitor reduced bacterial counts 50-fold. In essence, the inhibitor strips staph of its "golden armor," Oldfield says.