In war zones around the world, bandits steal food meant for starving civilians. One of medicine's most feared pathogens performs the same sort of piracy, new research suggests. To obtain the iron it needs to sustain itself, the bacterium Staphylococcus aureus steals the essential mineral from human blood cells. Chemicals that stop the banditry might offer a much-needed new type of antibiotic to kill dangerous drug-resistant infections.
S. aureus causes illnesses that range from ear infections to meningitis. Antibiotics that kill it are quickly losing their punch. Half of all hospital-acquired staph infections now resist all but one antibiotic, vancomycin. Some strains are learning to evade even that one, so new ways of killing the bug are needed urgently.
Nutrition is a possible weak point. S. aureus, like other bacterial pathogens and like us, needs iron to keep its engines running. A few years ago a team led by Olaf Schneewind, now of the University of Chicago, starved S. aureus for iron and caught one of its proteins red-handed: The protein had grabbed an iron-containing chemical called heme from hemoglobin, the protein that makes red blood cells red.
Now, Schneewind's postdoc Eric Skaar has unraveled a conspiracy between this protein and six others that enables the microbe to pilfer iron from human red blood cells. Collectively these proteins are known as iron-regulated surface determinants, or Isd proteins. After a S. aureus protein punches holes in the red blood cell, Isd proteins form a bucket brigade that steals heme from hemoglobin and pries off its iron to nourish the bacterium, Skaar, Schneewind, and colleagues report in the 7 February issue of Science. They also identified two other proteins called sortases that tie Isd proteins to the cell wall so they can do their jobs. That means drugs that block the pathway, perhaps by blocking sortases, might keep even the nastiest S. aureus strains from getting the iron they need to grow, Skaar says.
"I liked [the study] very much," says microbiologist Klaus Hantke of the University of Tübingen in Germany, adding that it offers the best description yet of how a bug extracts iron from heme. But S. aureus and other microbes have backup plans to obtain iron, he cautions, so blocking them from stealing heme iron might not kill them.