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The development of innovative antibiotics is urgently required to combat the spread of antibiotic-resistant infectious diseases, especially hospital-acquired infections. In direct response to this unmet medical need, groups at the NIBN are developing both synthetic and naturally-occurring molecules to prevent a phenomenon termed Quorum Sensing (bacterial communication). In particular, such molecules are assayed for bioactivity in preventing biofilm formation, a major bacterial resistance mechanism that envelops bacteria rendering them far less susceptible to antibiotics. Other anti-bacterial activities efforts are focused on screening libraries for inhibitory activities targeting bacterial-specific, proteolytic degradation pathways known to be critical for bacterial virulence. Such a strategy is used to specifically derail infectivity associated with Myobacterium tuberculosis infections (via inhibition of a unique pupylation pathway) and E. coli, Klebsiella, Vibrio Cholera and Pseudomonas aeruginosa (via inhibition of Lon protease). Additional activities within the infectious disease group concern host-pathogen co-evolution concerning T and B-cell immunodominance, HLA binding prediction and how all this information can be leveraged for rational vaccine design. Furthermore, research concerning the cell abscission component of cytokinesis, namely the ESCRT machinery, is being adapted in understanding the process of viral budding and infection and how such a process can be arrested with specific inhibitors.

 

Group members