Mycobacteria Infection Model to Accelerate Search for Treatment

Researchers in Australia have successfully engineered human immune cells to model mycobacteria infection, which is common among immunocompromised individuals. The breakthrough paves the way for new drug testing and treatments against the opportunistic infection, which to date has limited options because of a lack of infection models to test new drugs.  

Eleven percent of children with cystic fibrosis test positive for mycobacteria. Current treatments take months and involve cocktails of different antibiotics with wide-ranging toxicities, but often fail as the infection is highly resistant to antibiotics. Patients with mycobacteria are also excluded from receiving life-saving lung transplants. And, due to high treatment failure rates, repeated cycles of infection can greatly damage the lung tissue and accelerate progression of lung failure in those with cystic fibrosis. 

“Improved treatments could mean less frequent hospital visits, shorter stays and minimal exposure to toxic antibiotics, which is particularly important for children with cystic fibrosis,” says Dr. Sohinee Sarkar of Murdoch Children’s Research Institute.

Led by Murdoch Children’s, the team used stem cell technology to better understand how the infection invades immune cells and causes health complications, such as lung and skin and soft tissue infections, in immunocompromised people, particularly those with cystic fibrosis. The immune cell type they created, known as a macrophage, plays an important role in infection, inflammation and regeneration. For this reason, it is also a natural host for germs.

“Using our stem cell-made immune cells, we successfully infected them with a germ called mycobacteria. We could see where these mycobacteria live inside human immune cells and the immune reactions they triggered,” says Murdoch Children’s researcher Dr. Shicheng Jacky Sun. “We were also able to use our stem cell model to rapidly test and screen different types of antibiotics against mycobacterium.”

Dr. Sarkar said the infection model could also be used for drug screening for other superbugs with limited treatment options. “Some bacteria have evolved to escape our immune system by hiding themselves within host cells, making it difficult to treat these infections with traditional antibiotics,” she said. “Our stem cell-based infection model can be readily scaled up to screen large number of drugs against such bacteria to identify new treatments.”

Researchers from the University of Melbourne and Monash University also contributed to the findings, which were published recently in the journal Stem Cell Reports.