STRUCTURAL BIOLOGY OF BACTERIAL PATHOGENESIS

Abstract: 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 the characterization of different

pharmacological targets with new potential drugs.

6) Structural characterization of spore germination and development of novel inhibitors against C. difficile infections.

7) Proteins involved in bacterial flagellum decoration.

8) Proteins involved in neurodegenerative disorders.

9) Autolysins S. aureus

10) Chromosome segregation in S. aureus.

11) 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.

12) Phage Proteins to Tackle Infectious Diseases.

13) Developing New Agonists for the treatment of Drug-Resistant Bacterial Infections

14) Proteins involved in Sponge immunity.