Structural characterization of complexes involved in bacterial cell wall elongation

• Grant number: 19/27148-4
• Support type: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): April 01, 2020
• Effective date (End): January 31, 2022
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Andrea Dessen de Souza e Silva
• Grantee: Fernanda Angélica Sala
• Home Institution: Centro Nacional de Pesquisa em Energia e Materiais (CNPEM). Ministério da Ciência, Tecnologia, Inovações e Comunicações (Brasil). Campinas , SP, Brazil
• Associated research grant: 17/12436-9 - ANTIBIO-BAC: exploring the bacterial cell wall as a target for novel antibiotherapies, AP.SPEC

Abstract

The bacterial cell wall defines morphology and protects bacteria from external stress. Biosynthesis of its major component, peptidoglycan, occurs via a complex and dynamic process involving protein-protein interactions between PBPs (Penicillin Binding Proteins) and members of the elongasome. Due to the emergence of antibiotic resistant pathogenic bacteria, the development of new drugs and the identification of new molecular targets have become crucial. Due their critical hole in cell viability, the complexes that participate in the PG synthesis pathway have become potential targets. However, its structural characterization has been a great challenge due to the transitory character of the interaction between the components. Dr. Dessen's group recently published the first crystallographic structure of proteins involved in elongasome - the PBP2:MreC complex. We believe that the experience gained in the characterization of the binary complex can be extrapolated and modified in order to explore new interactions. In this project, we propose to study the combinations between MreC:PBP2 and class A PBPs, as well as the interaction of PBPs with the lytic transglycosylase - MltA and the periplasmic protein MipA. The complexes will be studied for H. pylori, A. baumannii and P. aeruginosa and characterized by biophysical techniques. Once the best purification conditions are established, the samples will undergo crystallization and/or cryo-microscopy tests. We believe that the structural characterization of different complexes will allow a better understanding of bacterial cell wall biology and may impact on biological and health care. (AU)