The human body fights staph infections by starving it of essential nutrients. Staph, it turns out, is remarkably good at changing what’s on the menu.
Staphylococcus aureus — the infamous agent behind MRSA and most staph infections — needs sulfur to build proteins and other materials essential for survival. In a new Michigan State University study, now published in the Journal of Bacteriology, researchers found the bacterium can adjust its diet depending on what sources remain available.
Understanding how S. aureus finds the nutrients it needs to survive could eventually reveal new ways to weaken the bacterium, potentially making antibiotic-resistant infections easier to treat.
The team, overseen by Neal Hammer, associate professor in MSU’s Department of Microbiology, Genetics and Immunology, found that S. aureus can adjust its inner workings in response to any one of a number of different sulfur-containing compounds — like cysteine, glutathione or thiosulfate.
The research was supported by the National Institutes of Health and led by Paige Kies, then a graduate student in Hammer’s lab. Kies is now a researcher with the Infectious Diseases Research Laboratory at the Mayo Clinic.
“Many people think of bacteria as simple organisms, but this study shows that S. aureus can effectively ‘change its diet’ depending on what’s available,” Hammer said. “It monitors its environment, activates different genetic programs and switches between nutrient sources to keep growing.”
Switching sulfurs
Previous research had shown that much of this sulfur-sensing behavior is controlled by a regulator protein called CymR, which acts as an on-off switch for sulfur-acquisition genes. CymR keeps the genes turned off until the bacteria’s sulfur supply runs low. In the new study, Hammer’s team found that when starved of sulfur, the bacteria switch on hundreds of genes, far more than CymR controls, triggering other, related metabolic pathways like iron acquisition and oxidative stress defenses that also help the bacteria survive hostile conditions.
When the team compared the bacteria’s response to different potential sulfur sources, one unexpectedly stood out. When S. aureus had access to thiosulfate, it triggered a cascade of changes, activating far more genes than when it had access to other sulfur sources. This finding helped the team pin down the specific function of a transporter protein the bacteria use to grow on thiosulfate.
“When staph infects people, it’s basically eating us,” Hammer said. “But the question is: What’s on the menu? These studies get us closer to understanding not only staph, but also the metabolites that change within our bodies in response to infection.”
Fuel and armor
Hammer’s team also discovered that some of the sulfur-containing compounds give the bacteria more than just nutrition. They found that glutathione, one of the sulfur sources tested, helped shield the bacteria from toxic forms of iron and from hydrogen peroxide, which the immune system uses to fight invading microbes.
“Sulfur is not simply food for the bacterium,” Hammer said. “The same sulfur-containing molecules that provide nutrients also help protect the cell from potentially lethal stresses. In other words, the bacterium uses sulfur both as fuel and as armor.”
That dual role helps explain how S. aureus can keep growing even in the hostile environments it meets inside the human body.
The team’s next steps: determine which sulfur sources S. aureus relies on during real infections and whether blocking its access to them could make infections easier for the immune system, or antibiotics, to clear.
As antibiotic resistance continues to spread, understanding exactly how an infectious bacterium like S. aureus feeds itself gives researchers one more piece of the puzzle in the ongoing search for new ways to fight it.
