Research team
Expertise
Bacterial infections play a significant role in various lung diseases, including community-acquired pneumonia. To infiltrate the lungs, bacterial pathogens produce numerous proteases that are essential for functions such as cell viability, physiology, and virulence. One such example is Streptococcus pneumoniae, which relies on various virulence factors, including the serine-based high-temperature requirement A protease (HtrA). The HtrA protease activity is critical for breaking down biofilms and promoting competence, a crucial step in the development of multi-drug resistant strains. However, our understanding of the molecular mechanisms governing SP-HtrA's proteolytic activity during different infection stages remains incomplete, primarily due to the limited methods available to study HtrA protease activity. This understanding is not only essential but also timely, given the increasing multidrug resistance among pathogens. Several lines of evidence indicate that proteases, in general, play a crucial role in pathogen survival and colonization. Therefore, elucidating the previously unknown virulent roles of these proteases is vital, as it can lead to the discovery of novel therapeutic targets or approaches. Consequently, my research at the University of Antwerp is divided into two main components: The development of highly sensitive and selective activity-based probes (ABPs) through activity-based protein profiling. These ABPs will covalently modify the active site of the protease, enabling the real-time monitoring of protease cleavage in living cells and tissues. The application of these ABPs, following biochemical validation, in in vitro and in vivo infection models. This project involves various techniques, including solid-phase peptide synthesis, organic synthetic chemistry, biochemical methods, protein expression and purification, proteomics, and imaging, among others.