Mimicking bacterial growth to fight antibiotic resistance
Two Illinois State University professors of biology are helping develop ways to mimic the way bacteria usually grow in the human body in an effort to help scientists understand what makes some bacteria resistant to antibiotics.
“In a way, all of the physiology on bacteria is being done wrong when we grow bacteria in laboratory media,” said Illinois State’s Research Professor of Microbiology Brian Wilkinson. “It’s not how they grow in the body.”
Wilkinson has long studied antibiotic resistance in pathogens—or strains of disease that don’t respond to antibiotics. He is teaming up with Illinois State’s School of Biological Sciences Director Professor Craig Gatto to introduce a certain type of unsaturated fatty acid into the mix of studying bacteria. The duo are on the second year of a two-year, $275,000 grant from the National Institutes of Health for their work.
There are a lot of fatty acids in the human body in various forms. These fatty acids include both saturated fatty acids—which make butter solid at room temperatures—and unsaturated fatty acids—such as oleic acid that makes olive oil liquid. Fatty acids are also present in the cell membranes of pathogenic bacteria such as Staphylococcus aureus.
The problem comes with the shape of fatty acids the bacteria produce when they are grown in the lab, noted Wilkinson. “Bacteria have two types of fatty acids in the molecules of their membranes: straight-chain fatty acids and branched-chain fatty acids. Straight-chain fatty acid look like this,” he said, holding his hand in a flat, vertical line. “While branch fatty acids ‘branch’ out at the end, which gives a certain degree of fluidity to the membrane.”
When growing in the body in an infection, staph takes advantage of the fatty acids already there and use them to make their membranes—it’s cheaper and easier for them. They particularly like oleic acid, which they cannot make for themselves. “We’re studying the situation much closer to what bacteria will look like in an infection,” said Wilkinson. “It may alter the antibiotic susceptibility of the bacteria.”
Gatto noted the research allows scientists the chance to work toward a common goal. “One of the exciting opportunities available at Illinois State is the ability to collaborate with colleagues working in areas very different from your own,” said Gatto, a protein biochemist who has spent a career studying structure and function of membrane proteins.
Lab tech Gloria Alvarado calls the work exciting. “I feel I’ve learned a lot from Brian in regards to lab techniques and how to approach a scientific question,” said Alvarado, who earned a bachelor’s degree in molecular biology and a master’s degree in biology from Illinois State.
Alvarado and Wilkinson cultivate the bacteria in the different growth conditions, isolating various lipid molecules before sending samples off to research partners at the University of Washington in Seattle for analysis of lipid chemistry and the University of North Carolina in Wilmington for biophysical analysis. “We are also studying the effects of different lipid compositions on antibiotic resistance here at ISU,” said Wilkinson.
Gatto noted that in his area of expertise, the importance of lipid composition has long been appreciated. “Thus, it is not surprising that our work is revealing that bacteria able to incorporate and exploit host lipid molecules to their advantage have been positively selected for over time,” he said.
Wilkinson hopes the studies prompt more scientists to look at the growth medium for bacteria, and how that might impact how the disease develops. “They could say, ‘Well, we might want to add some of these fatty acids to a medium in order to mimic the host conditions better,’” he said.
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