STRUCTURAL BIOLOGY OF BACTERIAL PATHOGENESIS

This proposal focuses on proteins, enzymes and macromolecular complexes pivotal in the following fields of bacterial pathogenesis and immunity:
1- bacterial Surface proteins involved in virulence and host-pathogen interactions. The objective is to identify and to characterize novel surface proteins from human pathogens and to unveil their implications in virulence and host-pathogen interactions.
2- Antibiotics resistance mechanisms in multi-drug resistant pathogens. We have
discovered an unprecedented allosteric mechanism for antibiotics resistance in MRSA and we will explore (i) how the mechanism is triggered, (ii) how the key proteins in this process interacts with other partners and (iii) other related proteins that could present similar mechanisms. We also intend study the origin of beta-lactamase resistance in some G(-) pathogens.
3- Peptidoglycan (PG) recycling and cell wall remodelling. We intend full characterization of the mechanism of PG process in G(-) bacteria that involves periplasmic and cytoplasmic
proteins. PG recycling is critical in activation of beta-lactamases and virulence. Also, study of cell- wall modification during sporulation and insertion of cell components like pili is intended.
4- Macromolecular machinery of bacterial divisome. We have recently reported the essential proteins in pneumococcal division PcsB, FtsE, ECD-FtsX and LytB. Now we intend to decipher the interaction of these proteins with other partners and also to characterize all the proteins involved.
5) New drugs and therapeutic tools against diseases. We intend characterization of different pharmacological targets with new potential drugs.
6) CRISPR-Cas Ring Nucleases are critical enzymes for bacterial immunity since they are responsible for switching off the abortive infection defence mechanism triggered during viral infection therefore halting the cell death process