Researchers at Dartmouth Medical School have discovered a new model to study antibiotic-resistant bacteria found in cystic fibrosis patients. DMS professors George O'Toole and Bruce Stanton recently outlined their findings in the April issues of Infection and Immunity and the American Journal of Physiology: Lung and Molecular Physiology.
Cystic fibrosis is a genetic mutation that causes lung cells to release more iron into lung fluid, and the buildup promotes bacteria growth, according to Stanton. Bacteria latch onto iron, using it to become resistant to antibiotics and reproduce rapidly. The mutation thus predisposes patients to further lung damage and early death. The average life span of a cystic fibrosis patient is 38 years.
For the first time in cystic fibrosis research, the DMS team developed a model to grow biofilms -- bacteria communities -- on lung cells in the laboratory. They tested the cells' response to tobramycin, the antibiotic routinely prescribed to fight the infections.
"There were two different, related findings [from the model]," O'Toole said. "We've developed a model system that we think replicates conditions found in cystic fibrosis that allows you to make highly antibiotic resistant communities in the lab. On the flip side of the finding, we can see that resistance is much higher than expected from our and other labs' previous published work."
Studying the bacteria growth on lung cells, researchers discovered that even 10 times more antibiotics than the amount that is safe for patients could not effectively kill the bacteria communities. Previous models facilitated biofilm growth on plastic or glass.
"We realized bacteria develop much faster and are more resistant to antibiotics than known from studies of biofilms grown on plastic," Sophie Moreau-Marquis, a postdoctoral fellow to Stanton, said. "To develop new treatments we need to study the right model."
The key problem for cystic fibrosis researchers is to develop effective medicine for patients, O'Toole said. The solution may be found in a combination of existing drugs, according to Stanton.
"We think we've identified two drugs that are already FDA approved," Stanton said. "Individually they don't work but together they act synergistically to eliminate infection. Since they are approved, we don't need to develop new ones so it is easier, faster and cheaper to get approval."
Developing new drugs can take ten to fifteen years and cost over $1 billion, Stanton said.
Stanton studied the success of drug combinations in his lab, but said the only way to be certain of the two drugs' efficacy is through clinical studies. Stanton would not disclose the names of the drugs due to the confidential nature of his work.
Researchers believe they have located a specific gene that regulates the strength of the imposing bacteria, which may help them find a cure, according to Gary Anderson, a post-doctorate fellow in O'Toole's lab.
The effect of cystic fibrosis on children motivated the approximately sixty researchers at DMS who study the infection, according to Moreau-Marquis.
"As far as I'm concerned [cystic fibrosis] is a disease of children," Moreau-Marquis said. "When you go to seminars you realize how much they are affected and want to make a difference. As a parent and a scientist, it makes sense."
