Scientists Follow the Staph Trail to Find Human Susceptibilities
Scientists have finally found an answer to one of the great mysteries about the most deadly bacteria, Staphylococcus aureus — why it attacks primarily humans and not animals. And they now have an idea of why some humans are particularly susceptible to these bacteria that kill 100,000 Americans a year, far more than any other microbe.
In a study released on Wednesday, researchers at Vanderbilt University report that staph evolved to zero in on particular regions of human hemoglobin so it could burst the cagelike molecule and feed on the iron inside. People who are resistant to staph, they suspect, might have slight genetic variations that tweak the hemoglobin regions the bacteria seek, making them impervious to the attack.
The work is part of a more general look at genes and disease. With new tools to look in detail at slight genetic variations, researchers are asking why some people get some diseases and others do not and why some die from diseases that others almost shrug off. With staph, for instance, 30 percent of the population harbors the bacteria in their noses, with no signs of infection.
Staph experts say the discovery, published in the Dec. 16 issue of Cell Host & Microbe, answers a lot of questions about the bacteria and shows them new directions for research.
“It’s terrific work,” said Frank DeLeo, acting chief of human bacterial pathogenesis at the National Institute of Allergy and Infectious Diseases. “It really is moving the field forward.”
The work began in 2002 when Eric P. Skaar was a postdoctoral fellow and fascinated by staph.
“Staph is the worst infectious threat to public health,” he said. “It is the No. 1 cause of heart infections and skin infections, the No. 1 cause of soft tissue infections. It is a big cause of pneumonia. It is the No. 1 hospital acquired infection.”
The bacteria can take up residence in any tissue of the body, he added.
Staph, he said, “is sort of a creepy bug.”
But it, like all organisms, needs iron, and Dr. Skaar wondered how it got it. The answer, he discovered, is that the bacteria “pop open red blood cells and grab the iron.”
Now, as an associate professor at Vanderbilt, Dr. Skaar asked a question no one had thought to ask before: Do the bacteria like some hemoglobins more than others?
He grew staph in the lab, giving them blood from different animals, from mice to baboons to humans. Staph definitely preferred human blood, he reported in the new paper, but there also was a definite trend, the higher up the evolutionary scale an animal was, the more the bacteria liked its blood.
Then Dr. Skaar and his colleagues found the protein on staph that attaches to hemoglobin and discovered that it grabs onto segments of the blood protein that are specifically in humans. It can attach to similar segments in animal hemoglobins, but less avidly.
Finally, the researchers infected two strains of mice. One was normal lab mice, with normal mouse hemoglobin. The other had half human hemoglobin and half mouse hemoglobin. The strain with human and mouse hemoglobin had 10 times as much bacteria growing in its organs.
That explains why it has been so frustrating to study staph infections in mice, said Mark S. Smeltzer of the University of Arkansas for Medical Sciences. Researchers use mice, which are cheap and readily available, to study treatments and vaccines for staph. But it has been so hard to infect them — scientists have to inject them with so many bacteria, Dr. Smeltzer said, that “to my mind it is unrealistic.”
It was just so much more than were required for many, if not most, infections of humans, he explained. The new study explained why and suggested a way around the problem — using mice with human hemoglobin — he added.
But, for Dr. Skaar, the result also suggested an answer to one of the most pressing questions about staph infections in people: Why do one-third of the population have the bacteria in their noses and not get sick while, for others, a staph infection can be lethal?
“In my opinion, that is the most important question in Staph aureus biology right now,” Dr. Skaar said.
His work, he said, suggests that there are genetic factors that determine susceptibility to infection between species. Are there also genetic factors that determine susceptibility within a species, the human species?
He has a way of finding out. There are well-characterized minor genetic differences in hemoglobins among different people. And Vanderbilt Medical Center has a gene bank with the DNA of thousands of its patients. Dr. Skaar is using that gene bank now to look at the hemoglobin genes of all the patients who had staph infections and compare them with the gene sequences of patients who were not infected. He expects that if there are variations among human hemoglobins that determine susceptibility to staph, he is likely to find them.
His hope, he said, is that in the future a patient will come to a hospital and, as part of a routine work-up, doctors will determine from the person’s hemoglobin whether to worry about staph. Those who are susceptible would get intravenous antibiotics before risky procedures like surgery.
“That’s the most exciting possibility,” Dr. Skaar said. “Just knowing you were more susceptible would be very valuable.”
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