Regulated degradation of proteins impacts all cellular processes and helps remove damaged or misfolded proteins, especially during cellular responses to various stressors. Proteasomes carry out the vast majority of the degradative functions in eukaryotes and archaea, but in bacteria are only found in the actinomycete lineage. This proposal aims to characterize a novel putative protein degradation machinery present in a number of bacteria, using the opportunistic pathogen Pseudomonas aeruginosa as a model. This will be achieved through two specific goals: 1. a thorough investigation of the structure and function of this putative protease. 2. Demonstration of its importance in processes that govern P. aeruginosa infection. Given the importance of this organism in the pathology of wound infections, among the numerous infections it causes, these studies will uncover bacterial protein degradation pathways that control infectivity and thereby impact normal wound healing. This approach will enable the identification of novel therapeutic targets for human disease states caused by pathogens, like P. aeruginosa, that rely on these protein degradation pathways.
Protein degradation impacts virtually every cellular process and is already an important drug target in humans. In this work, we will characterize novel protein degradation machinery in the opportunistic pathogen Pseudomonas aeruginosa, which commonly infects wounds, and demonstrate its importance in processes vital to infection by this bacterium. Understanding this novel protein degradation machinery, and its role in infection, can serve as a starting point to develop new antibacterial therapies.
| Jashnsaz, Hossein; Al Juboori, Mohammed; Weistuch, Corey et al. (2017) Hydrodynamic Hunters. Biophys J 112:1282-1289 |
