November 10, 2014—Scientists have identified thousands of species of microbes that live in and on the human body. Although microbes can cause disease and infections in humans, they aren’t always harmful. Assistant Professor of Biology Shaun Brinsmade is looking at when and how microbes turn from harmless to harmful.
Brinsmade’s laboratory studies Staphylococcus aureus (S. aureus), the bacterium associated with “Staph” infections and MRSA (Methicillin-Resistant Staphylococcus aureus). About 20 to 30 percent of humans consistently carry S. aureus in their noses, Brinsmade says. But the bacterium can also be acquired from other people, whether in a hospital or a community. Although scientists are uncertain if S. aureus can be beneficial to humans, the microbe often exists in the body in a commensal state, meaning that it causes no ill effects to the host.
A microbe’s change from commensal to harmful is the current focus of Brinsmade’s research. “At some moment, there’s a switch that is triggered,” Brinsmade said. “The mechanisms by which that switch occurs are unclear right now.”
According to Brinsmade, many factors likely contribute to this change—factors in both the bacterium and the host. This change may be due, in part, to nutrient availability. S. aureus gets nutrients from the human body in the form of amino acids and sugars. But S. aureus is competing for limited resources with other microorganisms.
“When bacteria run out of nutrients, they turn on some of their most important virulence genes,” Brinsmade explained. “These are the genes that produce the factors that allow them to cause what we perceive as disease or infection,” he continued.
In a recent article in the Proceedings of the National Academy of Sciences (PNAS), Brinsmade examined CodY, a transcription factor and protein, which may be one piece of the S. aureus puzzle. “CodY provides a link between nutrient availability and the activation of disease-causing factors,” he said.
CodY is a DNA-binding protein. When bound to different sites on the chromosome in S. aureus, CodY helps prevent expression of virulence genes. But when the cells are starved for nutrients, CodY begins to come off the chromosome. “If you can keep CodY active in a condition where it might go inactive [and release from the chromosome], then you can keep those virulence genes shut off.”
In the study published in PNAS, Brinsmade and his team presented a methodology for investigating when and where CodY released from the chromosome in a related bacterium Bacillus subtilis. “This method took a couple of years to work out the kinks and get all of the experimental design worked out,” he explained. “We were trying to determine the firing sequence for genes controlled by CodY.”
Brinsmade and his team are now planning to apply the same methodology to S. aureus.
Determining the timing in this change from harmless to harmful is essential, Brinsmade says, in order to understand S. aureus. With more knowledge about how S. aureus behaves, scientists may then be able to build a framework for new drug therapies for the bacterium, which can be resistant to antibiotics.
Brinsmade describes S. aureus as a “clever” and “opportunistic pathogen,” but he stresses that microbes may only be doing what they need to do to survive. “Most likely they are only trying to make a metabolic living,” he explained. His research contributes to the understanding of the trillions of microbes that live not only on the human body, but in our soil and oceans as well.
“By and large, the vast majority of the microbes on this planet are not those that make us sick. We have only scratched the surface to what microbes are out there, and more of them are harmless or even beneficial to us,” he continued.
Although scientists know that microbes can have practical applications in medicine and biofuels, Brinsmade hopes the study of microbiology will lead to applications we haven’t even thought of yet.
“All we can do is continue to study microbes, learn about new organisms, and see what their capabilities are. Only a few of them are the ones that make us sick, and you have to remember that.”
Undergraduate students interested in laboratory research opportunities should visit the Brinsmade Lab website for more information.