Structural study of the substrate delivery mechanism of the Type II Secretion Syst...
| Grant number: | 18/04344-0 |
| Support type: | Scholarships in Brazil - Doctorate (Direct) |
| Effective date (Start): | April 01, 2018 |
| Effective date (End): | December 31, 2021 |
| Field of knowledge: | Biological Sciences - Biochemistry |
| Principal Investigator: | Andrea Dessen de Souza e Silva |
| Grantee: | Yuri Rafael de Oliveira Silva |
| 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 |
| Associated scholarship(s): | 19/20836-2 - Structural study of the substrate delivery mechanism of the Type II Secretion System of Acinetobacter baumannii, BE.EP.DD |
Abstract Acinetobacter baumannii is a nosocomial pathogen accountable for millions of hospital-related infections per year in impaired patients. This pathogen has become more relevant in the last few years due to high rates of antibiotic resistance associated to it, leading it to the World Health Organization (WHO) priority list of bacteria for the development of new antibiotic treatments. Its infection and toxicity mechanisms are poorly understood in comparison to other pathogens, what makes it harder to develop new treatments against this microorganism. A. baumannii has a Type II Secretion System (T2SS) involved in pathogenicity, which exports the protease CpaA and the lipase LipA to the extracellular environment, however the roles of these effectors in infection are not stablished yet. These proteins depend on chaperones on the periplasm (CpaB and LipB, respectively) to be exported, another unexplained fact. The goal of this project is to characterize structurally the proteins CpaA and LipA in the presence and absence of their chaperones, CpaB and LipB, contributing to the elucidation of the transport mechanism in T2SS and of their roles in pathogenicity. We are going to clone, express and purify the enzymes and their chaperones so we can perform crystallization assays and x-ray diffraction to solve the tridimensional structures. The interaction between each pair of proteins are going to be studied using biophysical assays, and microbiological assays are going to be used to study their roles in virulence. These results will present the first informations in atomic-level detail about the effectors of T2SS in A. baumannii, and will open new doors for the development of new antibiotic treatments in the future. (AU) | |