Deciphering Mode of Bacterial Infections Could Help Cystic Fibrosis Patients Breathe Easier

Pseudomonas aeruginosa may be the leading cause of fatal lung infection in young adults with Cystic Fibrosis (CF), but researchers in the Department of Molecular and Cellular Biology (MCB) are making strides in understanding how this bacteria causes infection – the first step to helping CF patients breathe easier.

A team led by Prof. Cezar Khursigara, in collaboration with the Hospital for Sick Children in Toronto, has discovered that a defective gene known as SLC6A14 could play a role in enabling P. aeruginosa bacteria to attach to the airways of CF patients.                                                 

“We were all super excited throughout the project,” says Khursigara. “We knew after the first experiment that the hypothesis was sound.”

Postdoctoral fellow Amber Park, working with Michelle Di Paola at the Hospital for Sick Children, led the efforts on what was a new area of research for the Khursigara lab.

Chronic P. aeruginosa infection typically happens when CF patients are between 18 and 22 years of age, but individuals with a defective SLC6A14 gene tend to become infected as early as 12 years of age – a drastic and life-altering difference.

Using both cell and animal models, the research team investigated whether defects in the SLC6A14 gene affect how and when P. aeruginosa attaches to cells in the airways leading to the lungs. After discovering that the SLC6A14 gene encodes a transporter that helps move arginine, an amino acid naturally found in the body, away from human airways, they hypothesized that a defect in the gene would lead to increased arginine in the airways.

The team found that the defective SLC6A14 gene did indeed lead to increased levels of arginine, as well as increased P. aeruginosa attachment in the airways. Because arginine can act as a nutrient for bacteria, the researchers think that this could explain the earlier lung infection seen in patients with the defective gene.

“Any information we can get in terms of helping people with chronic infections and cystic fibrosis to potentially be able to breathe better is what keeps us motivated,” says Khursigara.

He and his team have already begun follow-up work, and hope to soon use even more clinically relevant strains of the bacteria to ask detailed questions about its behaviour - for example, whether or not the location of bacteria development in the airways can be predicted.  By gaining a better understanding of the mechanism of bacterial attachment and infection, their ultimate goal is to bring personalized treatments for CF patients closer to reality.

This research was funded by the Natural Sciences and Engineering Research, Cystic Fibrosis Canada, and the Canadian Institutes of Health Research.

Read the full article in the journal mBIO.

Read about other CBS Research Highlights.