Mines researchers explore structure of staph bacteria to develop new treatment options
“The buzzword is rational drug design – we’re being very deliberate about the protein we’re targeting and the inhibitors we’re building," says Chemistry's Christine Morrison
Researchers at Colorado School of Mines have structurally characterized for the first time key proteins that could be used to develop new treatment options in the fight against drug-resistant staph infections.
Dr. Christine Morrison, assistant professor of chemistry, and her research team collaborated with colleagues at Rutgers University to map out two specific proteins in Staphylococcus aureus (S. aureus) that are essential to the bacteria. In this context, essential means that without these proteins – the cysteine desulfurase SufS and the sulfurtransferase SufU – the bacteria cannot survive.
“Now that we know the structure of these proteins, we can start to rationally design drugs to inhibit them and fight drug-resistant staph infections,” Morrison said. “Our ultimate goal is to create new classes of antibacterial agents to help mitigate the antibiotic resistance crisis.”
The researchers’ findings were recently published in the journal ACS Omega.
Morrison described the protein’s function within the bacterium like that of a door within a house.
“Proteins all have functions, just like doors have functions – they swing open and shut in order to allow or cut off access. If you put a door stop under the door, you prevent it from functioning, but the door stop has to be the right shape,” Morrison said. “Similarly, if we know what the protein looks like, we can create better door stops, or inhibitors, that prevent that specific protein from working without impacting surrounding human proteins.”
In this case, humans have their own version of the pathway, but that version is very different than what is present in Staphylococcus aureus
“Based on the structure of the protein, we have identified a drug discovery strategy that we’re executing right now where we have a library of small molecules and we’re seeing if they can inhibit this protein,” Morrison said. “The buzzword is ‘rational drug design’ – we’re being very deliberate about the protein we’re targeting and the inhibitors we’re building, rather than just throwing spaghetti at the wall.”
And while animal and human tests of any potential new drugs remain years into the future, the stakes could not be higher, Morrison said. A new class of antibiotics hasn’t been discovered since the 1980s.
“Bacteria are smart – they know how to evolve and get around our defenses,” she said. “There are many ways scientists are trying to develop new ways of killing bacteria. What I'm doing is trying to develop new drugs that target machinery in bacteria that have never been targeted before. It’s going to take all the approaches. We need to attack this challenge on all fronts.”
Lead author on the paper was Jesse Hudspeth, a PhD student in Morrison’s research group. Co-authors were Dr. Amy Boncella, a former postdoctoral researcher at Mines; current PhD student Emily Sabo; and Dr. Jeffrey Boyd and Taylor Andrews of Rutgers University.
Read the full paper, “Structural and Biochemical Characterization of Staphylococcus aureus Cysteine Desulfurase Complex SufSU,” at https://doi.org/10.1021/acsomega.2c05576.