“Individuals with cystic fibrosis have an impairment in their lungs where they have a hard time clearing out the mucus that accumulates within the lungs,” says Andreea Gheorghita, PhD candidate in the Department of Biochemistry at U of T.
Pseudomonas aeruginosa is a bacterium that causes opportunistic infections in individuals with weakened immune systems or other health concerns. For individuals with CF, repeated Pseudomonas infections often lead to long hospital stays and severe lung damage.
“Because of the impaired ability to clear mucus in the airways, these lung infections can become very persistent and prolonged, which eventually leads to lung tissue damage, loss of lung function, and eventually can cause patient mortality,” says Gheorghita.
Using the CMCF beamline at the Canadian Light Source (CLS) at the University of Saskatchewan (USask), the team has been able to visualize the interaction between two important proteins that are key players in Pseudomonas’s ability to make biofilm. This sticky secretion allows the bacterium to attach to the lungs and makes it difficult for antibiotics and the patient’s immune system to fight the infection.
“If we can try to prevent the biofilm and the bacterial pathogenic infections, we would have an opportunity to prevent the lung damage,” says Dr. Lynne Howell, Senior Scientist in the Program of Molecular Medicine at The Hospital for Sick Children and Professor in the Department of Biochemistry at U of T.
Howell says proteins in biofilm production are great targets for new drug therapies because you can stop the attachment of the bacteria, enhance the efficacy of antibiotics, and allow the immune system to take care of the infection.
Howell and Gheorghita say that they couldn’t do their research without the help of a synchrotron.
“As a national facility, the CLS provides a critical component to our research,” says Howell. “Without it, we wouldn't have been able to discover the key things that are now the focus of follow-up studies.”
The scientists hope their findings will help inform the development of new therapeutics in the future.
Lynne Howell is a member of the Board of Directors of the Canadian Light Source
Gheorghita, Andreea A., Yancheng E. Li, Elena N. Kitova, Duong T. Bui, Roland Pfoh, Kristin E. Low, Gregory B. Whitfield et al. "Structure of the AlgKX modification and secretion complex required for alginate production and biofilm attachment in Pseudomonas aeruginosa." Nature Communications 13, no. 1 (2022): 7631. https://doi.org/10.1038/s41467-022-35131-6
Photos: Synchrotron | CMCF beamline | Gheorghita and Howell in the lab
Canadian Light Source