- Burnett School College of Medicine Communique Faculty News Infectious Disease Division Research
An estimated 30,000 people in the United States suffer from cystic fibrosis, a genetic disease that makes patients prone to persistent lung infections. One of the most debilitating and difficult to treat pathogens is Mycobacterium abscessus (MAB), which causes tuberculosis-like infections.
Dr. Kyle Rohde, an infectious disease researcher at the Burnett School of Biomedical Sciences, is working to develop more effective therapeutics to fight MAB and recently received a $200,000 grant from the Cystic Fibrosis Foundation to advance his research.
MAB is a “cousin” of tuberculosis and is considered an opportunistic infection, as it usually targets individuals with underlying respiratory conditions or impaired immunity.
“So cystic fibrosis patients are one of the key populations where you will see MAB infections,” Dr. Rohde said. “And in these patients, the infection is prolonged and insidious and even harder to treat than tuberculosis. The standard treatment is a year or two of taking multiple antibiotics, and there is only about 50% chance of getting cured.”
Dr. Rohde is hoping to develop more effective drugs to kill the bacteria that can become resistant to existing drugs. Current therapies target the physical structure of the bacteria such as the cell walls. Dr. Rohde’s research will focus on the genes that control the bacteria’s behavior.
“We want to figure out how are they still surviving somehow, what genes are important and what they are doing to keep the bacteria alive,” he said.
His study will use a gene-editing technology known as CRISPRi to weaken or deactivate the bacteria by turning off one or more genes needed for its survival.
“Basically, we plan to engineer strains of MAB bacteria that, upon addition of a harmless chemical compound, we could turn off a specific gene and see what happens,” Dr. Rohde explained.
“So the idea is, if we can dial that gene down and see that the bacteria becomes really sensitive or die, then we could develop an antibiotic that could activate or inhibit that same protein, that would make a more effective therapeutic drug.”
The second phase of the study will test the genetically modified strains of bacteria in animal models with cystic fibrosis symptoms such as mucus in the lungs and weakened immune systems.
He said results from the study would help scientists better understand drug resistance in bacteria, as well as identify specific genes that will make good targets for antibiotics for infections in general.
““Developing a CRISPRi system to manipulate specific genes during a real infection would let us study candidate drug targets and also identify factors required to survive the immune system,” Dr. Rohde said. ““And good animal models of Cystic Fibrosis would have a big impact not only on our MAB studies, but could be useful for studying other CF pathogens as well.”