Towards a deeper understanding of Burkholderia cenocepacia’s virulence

Cystic fibrosis (CF) is a genetic disease with an approximated birth prevalence of 1:2300 for non-Hispanic Caucasians. This disease is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, leading to the formation of a sticky mucus layer in the airways and the pancreas. Although the life expectancy of patients has been increased through improved diagnosis and healthcare, this disease remains incurable and leads to the acquisition of life-threatening lung infections. These infections are caused, among others, by opportunistic pathogens, for example Burkholderia cenocepacia(B. cenocepacia). This pathogen can cause the fatal cepacia syndrome, a lethal complication, and makes the patient unsuitable for the needed lung transplantation.

 

B. cenocepacia survives inside macrophages, and this survival depends on the secretion of virulence factors, among which two (metallo)proteases. So far, their extracellular function in pathogenesis is known for degrading human immunity-related proteins and tissue-related proteins. Despite their importance in virulence, relatively little is known about their exact structure, function and role in intracellular pathogenesis. In this study we will characterize these two metalloproteases, which are needed for its intracellular survival. In addition, proteases are amongst the top list of “wanted” enzymes and have applications in detergent, food and textile industries. During this project, the application of these proteases will be valorized for industrial use. So far, by modifying the recombinant expression of the proteases we could accomplish a shorter and less labor-intensive protocol of protein expression, leading to enough yield to decipher their specificity. The next steps of this project will be to study their intracellular targets, potential applications and decipher potential protease synergy.

Authors

Stijn De Waele (1)
Kris Gevaert (2)
Miguel Valvano (3)
Bart Devreese (1)

Organisations

Lab of microbiology, Protein research Unit, Ghent University (1)
Flemish Institute of Biotechnology, Center for Medical Biotechnology, Ghent University (2)
Wellcome-Wolfson Institute of Experimental Medicine, Queen's University Belfast (3)

Presenting author

Stijn De Waele, Teaching assistant, Ghent University
stijn.Dewaele@ugent.be
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